There is increasing evidence that neurotrophins (NTs) are involved in processes of neuronal plasticity besides their well-established actions in regulating the survival, differentiation, and maintenance of functions of specific populations of neurons. Nerve growth factor, brain-derived neurotrophic factor, NT-4/5, and corresponding antibodies dramatically modify the development of the visual cortex. Although the neuronal Elements involved have not yet been identified, complementary studies of other systems have demonstrated that NT synthesis is rapidly regulated by neuronal activity and that NTs are released in an activity-dependent manner from neuronal dendrites. These data, together with the observation that NTs enhance transmitter release from neurons that express the corresponding signal-transducing Trk receptors, suggest a role for NTs as selective retrograde messengers that regulate synaptic efficacy.