Because the actions of neurotrophic factors appear distinct from those of traditional growth factors and cytokines, it was long assumed that the neurotrophic factors utilized receptors and signaling systems fundamentally different from those used by growth factors operating elsewhere in the body. Recent advances in the understanding of the structure of the receptors for neurotrophic factors have unexpectedly revealed that they are in fact similar to the receptors used by the traditional growth factors and cytokines. The expression of the receptors for the neurotrophic factors is exclusively or predominantly in the nervous system; activation of these receptors in the context of the neuron allows these factors to display distinctive actions. While the precise roles of the neurotrophic factors and their therapeutic potential in various disease states still remain to be elucidated, this review describes studies on their receptor systems, their notable biological activities in the nervous system, and recent insights provided by targeted gene disruptions.