It is widely assumed that long-term changes in synaptic strength underlie information storage in the brain and, ultimately, behavioral memory. Recent years have seen a major effort to identify and analyze electrophysiological model systems in which particular patterns of neural activity give rise to such enduring changes. Most of this attention has been focused upon hippocampal long-term synaptic potentiation (LTP), in which brief activation of a set of afferents gives rise to a persistent increase in synaptic strength of the activated synapses. LTP is a broad term. It has come to mean any persistent increase in synaptic strength induced by a variety of mechanisms in a large number of locations in the nervous system. The purpose of the present review is to examine the opposite phenomenon, use-dependent long-lasting decreases in synaptic strength, which have been collectively termed long-term synaptic depression (LTD). Also a blanket term, LTD denotes depression induced according to a variety of synaptic modification rules, mediated by various electrophysiological and biochemical events, and occurring extensively in the nervous system.