This article is part of the Postsynthetic Modification of Metal-Organic Frameworks special issue. Metal–organic frameworks (MOFs) have become a prominent topic in inorganic and materials chemistry over the past 2 decades. In addition to their design, synthesis, and characterization, their potential utility in applications as far ranging as drug delivery to carbon dioxide capture has advanced interest in these porous solids among scientists in disciplines beyond chemistry and materials science. The earliest MOF studies largely focused on solvothermal synthesis and characterization, with a heavy emphasis on their potential use in gas storage, in particular for methane and H2. Most MOFs studied at the turn of the millennium were being synthesized using commercially available multitopic carboxylic acid ligands, or similar ligands that could be prepared in one or two synthetic steps. In time, this suite of organic ligands became highly limiting with respect to the types of MOFs that could be prepared, as well as restrictive in terms of the attainable chemical functionality and physiochemical properties. Efforts to enrich the chemical functionality and property scope of MOFs led to the development of postsynthetic modification (PSM) as an alternative approach to derivatize, transform, and otherwise elaborate on MOFs. The concept behind PSM involves the synthesis of a “parent” MOF lattice that is subsequently modified, generally in a heterogeneous manner, to obtain a “daughter” MOF derivative with added or altered functionality. This modification is ideally achieved without loss of crystallinity or porosity. Originally envisaged and proposed by Hoskins and Robson,(1) PSM was first independently reported by Lee et al.(2) and Kim et al.(3) in 1999 and 2000, respectively. After remaining dormant for about 6 years, PSM reemerged with a handful of reports in 2006–2007 and then with a very rapid growth in studies and interest starting around 2008–2009. Since that time, PSM has been a continuous area of investigation for MOFs and related materials such as covalent–organic frameworks. Indeed, PSM is now such a staple of MOF chemistry that it can be found in many new MOF articles, in some form, even when it is not the primary focus of the study. In addition to covalent PSM of the organic components of MOFs, that is, the linkers, many other related methods that involve modification of either the organic linkers or the metal center secondary building units (SBUs) have been described, including postsynthetic deprotection (PSD), postsynthetic exchange (PSE), and postsynthetic polymerization (PSP). Some of these methods and related techniques have been reported under other commonly used terminologies, such as solvent-assisted ligand exchange (SALE), solvent-assisted ligand insertion (SALI), and others. Most importantly, PSM and related methods have become a mainstay of modern MOF research and an indispensable tool for altering existing MOF materials or generating entirely new MOF constructs. With this historical perspective as a backdrop, we are happy to introduce this Inorganic Chemistry Forum, “Postsynthetic Modification of Metal-Organic Frameworks”, to highlight recent advances in the use of PSM of MOFs. Over the past 15 years, the field has grown substantially and has become a central feature in many MOF articles, including those focused on efforts to modulate gas sorption, introduce catalytic activity, stabilize MOF structures, and many others. As the field has expanded, so has the creativity of those utilizing PSM, with increasingly impressive reports of clever strategies and a broadening scope for what can be accomplished using this approach. In this Forum, recent advances in the field of PSM are collected together and some of today’s cutting-edge research is highlighted. Within the realm of “traditional” PSM, where the organic ligands of the MOF are modified, D’Alessandro et al. describe the incorporation of a donor–acceptor Stenhouse adduct within DUT-5 to produce a photoactive MOF (DOI: 10.1021/acs.inorgchem.0c03383). Richardson et al. take a pendant alkenyl group on a biphenyl ligand of an IRMOF-9 analogue and convert it, using a series of three PSM reactions, to an aziridine ring (DOI: 10.1021/acs.inorgchem.1c00862). This work demonstrates that PSM can be employed on MOFs in much the way that multistep synthesis can be performed on molecular species. Similarly, Queen et al. use multistep PSM on a zirconium-based MOF to install polyamines that can facilitate carbon dioxide capture, a major thrust area in energy and environmental applications of MOFs (DOI: 10.1021/acs.inorgchem.1c01216). In another environmentally relevant twist, Jing Li et al. convert neutral zirconium-based frameworks to cationic porous solids via PSM to obtain MOFs suitable for ReO4– anion removal from water, which serves as a nonradioactive analogue of 99TcO4–, a significant wastewater pollutant stemming from nuclear waste storage (DOI: 10.1021/acs.inorgchem.1c00512). MOFs have also been examined for biomedical applications, in particular the delivery of therapeutics. Alves et al. use “click” PSM methods to decorate the surface of MOF crystals with folic acid to enable the targeted delivery of curcumin, an anticancer drug, to tumor cells (DOI: 10.1021/acs.inorgchem.1c00538). In a departure from typical MOF PSM reactions, which occur between a solid-state MOF and a solution-phase reagent, Wanbin Li et al. describe the use of vapor-phase reagents to modify MOFs (DOI: 10.1021/acs.inorgchem.1c00284). Vapor-phase PSM reactions are much less common than those of solution phase, yet they represent another efficient and clean approach to achieving these materials transformations. In an exciting new direction for PSM to create MOF–polymer hybrids, Tao Li et al. report the use of reversible addition–fragmentation chain-transfer polymerization to achieve PSP coatings on MOFs. The outcome is the production of MOF@polymer particles that can be assembled into ordered monolayer thin films using Langmuir–Blodgett methods (DOI: 10.1021/acs.inorgchem.1c00949). On another front, Qiaowei Li et al. describe how simultaneous ligand exchange and installation reactions enable the topological transformation of a layered hexagonal MOF lattice (hxl) to a 3D fcu MOF (DOI: 10.1021/acs.inorgchem.1c01341). This work demonstrates that not only is PSM useful for enriching the functionality and properties of MOFs, but also it is becoming a viable strategy for designing and discovering new MOF structures. Other reports in this Forum focus on PSM reactions involving SBUs or other metal ion centers in MOFs. PSM has frequently been used to place metal centers within MOFs, as described by Dincǎ et al., who strategically install Pd(II) in a scorpionate-derived MOF (DOI: 10.1021/acs.inorgchem.1c00941). The geometry of the MOF enforces an unusual coordination geometry at Pd(II) that is not observed in the analogous molecular species. Once a metal center is incorporated into a MOF, by either direct synthesis or PSM, these metal centers can be further modulated using PSM. For example, Doonan et al. use anion metathesis reactions to exchange strongly coordinating chloride ligands from Cu(I) centers in a MOF with weakly coordinating anions (DOI: 10.1021/acs.inorgchem.1c00849). This exchange enables binding of carbon monoxide or ethylene to copper(I). These unusual adducts are characterized by X-ray crystallography and portend the use of these Cu(I) MOF centers for catalysis. Similarly, Wade et al. examine ligand exchange reactions at Zn(II) centers found in a MOF with Kuratwoski-type SBUs (DOI: 10.1021/acs.inorgchem.1c01077). These PSM exchange reactions are again relevant to the use of these Lewis acid sites as solid-state catalysts. In a report by Howarth et al., a rare-earth-based MOF, Y-CU-10, was transformed into other rare-earth ‘metalloforms’ by PSM (DOI: 10.1021/acs.inorgchem.1c01317). The Y ion in Y-CU-10 was replaced by PSM with La(III), Nd(III), Eu(III), Tb(III), Er(III), Tm(III), and Yb(III). In a related report by Horcajada et al., protic sites in an anionic MOF are replaced by PSM with alkali cations for use in fuel cell membranes (DOI: 10.1021/acs.inorgchem.1c00800). In addition to these experimental findings, Gagliardi et al. used density functional theory calculations to simulate the adsorption enthalpy and vibrational bands of carbon monoxide and nitric oxide ligands at Fe3O SBUs during dehydration and redox reactions (DOI: 10.1021/acs.inorgchem.1c01044). These simulations are important for interpretating the spectral data and building an underlying atomic understanding of the electronic state of metal ions and ligands within MOFs. PSM and related methods are valuable components of the MOF synthesis and functionalization toolbox. We anticipate that new and creative methods for MOF PSM will continue to emerge, expanding the reach and impact of this powerful approach. Advancing MOFs as catalysts is one likely area of continued pursuit, as the installation of increasingly sophisticated catalytic centers in MOFs surpasses those that can be realized in molecular species. PSM will also continue to be an important tool for merging MOFs with other materials, such as synthetic polymers and biomolecules, to create unique heterostructures and composites. Another challenge is controlling the distribution of PSM reactions within MOF crystallites and characterizing/mapping where these reactions occur with spaciotemporal control. The continued use of computational and spectroscopic methods will help to elucidate PSM reactions and the composition and features of MOFs that have been transformed by PSM. Ultimately, it is anticipated that PSM will be utilized in the bulk-scale synthesis and modification of MOFs, thereby showing the importance of the strategy, not only as a specialized research and laboratory-scale method, but also as an industrial-scale and technologically important approach for the commercial application of MOFs. We look forward to these, and other unanticipated discoveries, in the field of MOF PSM in the future. Nathaniel L. Rosi received a B.A. degree in chemistry in 1999 from Grinnell College and a Ph.D. in chemistry from the University of Michigan in 2003. After completing postdoctoral work at Northwestern University, he joined the faculty of the University of Pittsburgh where he is now a Professor of Chemistry. His research program focuses on the design and discovery of new materials, investigation of their chemistry, and development of the science for precisely controlling and understanding their atomic/molecular structures, properties, and functions. His laboratory examines both molecular and nanoparticle assembly and has discovered new classes of chiral nanomaterials, new levels of structural and functional complexity in MOFs, and new strategies for the creation of bioimaging probes. These materials have led to the exploration of new phenomena and scientific questions at the intersections of inorganic chemistry, materials, and nanoscience. Seth M. Cohen received B.S. and B.A. degrees in chemistry and political science in 1994 from Stanford University and a Ph.D. in chemistry from the University of California, Berkeley, in 1999. After completing postdoctoral work at Massachusetts Institute of Technology, he joined the faculty of the University of California, San Diego, where he is a former Department Chair and a Professor of Chemistry. His research program focuses on the design and discovery of new MOF materials and MOF–polymer composite materials and the development of postsynthetic methods for the medication of MOFs. His laboratory also has a program in the field of bioinorganic chemistry, where the team develops metalloenzyme inhibitors using fragment-based drug-discovery approaches. This article references 3 other publications.