Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) are two related forms of short-term synaptic plasticity of GABAergic and glutamatergic transmission, respectively. They are induced by calcium concentration increases in postsynaptic cells and are mediated by the release of a retrograde messenger, which reversibly inhibits afferent synapses via presynaptic mechanisms. We review here: 1. The evidence accumulated during the 1990s that has led to the conclusion that DSI/DSE rely on retrograde signaling. 2. The more recent research that has led to the identification of endocannabinoids as the retrograde messengers responsible for DSI/DSE. 3. The possible mechanisms by which presynaptic type 1 cannabinoid receptors reduce synaptic efficacy during DSI/DSE. 4. The possible modes of induction of DSI/DSE by physiological activity patterns, and the partially conflicting evaluations of the calcium concentration increases required for cannabinoid synthesis. 5. Finally, the relation between DSI/DSE and other forms of long- and short-term synaptic inhibition, which were more recently associated with the production of endocannabinoids by postsynaptic cells. We conclude that recent studies on DSI/DSE have uncovered a specific and original mode of action for endocannabinoids in the brain, and that they have opened new avenues to understand the role of retrograde signaling in central synapses.