Recent, exciting research in neurotrophic factors has significantly enhanced our understanding of their actions. Neurotrophic factors have been shown to have robust effects on neuronal survival and differentiation in vitro and in vivo and have been tested in animal models of human neurologic disorders. These studies have encouraged initiation of clinical trials of several neurotrophic factors for diseases of peripheral nerves and motor neurons. In this article, the author reviews the data for the actions of neurotrophic factors on peripheral nerves and motor neurons, the rationale for their use in clinical trails. The results of clinical trials of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor type 1 (IGF-1), three neurotrophic factors that have been tested in phase III studies, are also reviewed.