The involvement of neurotrophic factors in neuronal survival and differentiation is well established. The more recent realization that these factors also play pivotal roles in the maintenance and activity-dependent remodeling of neuronal functioning in the adult brain has generated excitement in the neurosciences. Neurotrophic factors have been implicated in the modulation of synaptic transmission and in the mechanisms underlying learning and memory, mood disorders, and drug addiction. Here the evidence for the role of neurotrophins and other neurotrophic factors-and the signaling pathways they activate-in mediating long-term molecular, cellular, and behavioral adaptations associated with drug addiction is reviewed.