Substantial progress has been made in studies on enzymes synthesizing UDP-glucose (UDPG) which is essential for sucrose and cell wall biosynthesis, and in an array of other processes, e.g. glycosylation of proteins and lipids. The enzymes include UDPG pyrophosphorylase, UDP-sugar pyrophosphorylase (USPase) and sucrose synthase (SuSy). Genes coding for those proteins are under complex spatial and temporal regulation, and are frequently coexpressed. Recent evidence for regulation of some of the UDPG-synthesizing proteins by posttranslational modifications and oligomerization, together with discoveries of novel isozymes and unexpected locations within a cell (including chloroplasts and mitochondria) have made the studies exciting, but complex. The enzymes differ in specificity for sugar and nucleotide portions of their substrates/products, and may be involved in distinct metabolic pathways, but also in signaling. Homology models for USPase and SuSy structures are presented, based on recent crystallization of structurally related proteins. Future challenges in research on UDPG-producing enzymes are underlined.