Since its discovery over thirty years ago, the role played by Nerve Growth Factor (NGF) in the development and maintenance of sympathetic and sensory neurons of the peripheral nervous system has been well established and extensively studied. In addition, the existing data suggest that NGF may offer neuroprotection to dorsal root ganglion neurons against drug- and diabetes-induced neurotoxicity. Based upon its neurotrophic and neuroprotective activities, the systemic administration of NGF has been proposed as a treatment for several types of neurodegenerative diseases including diabetic neuropathy. The cloning of the human gene and the subsequent large-scale production of recombinant human NGF (rhNGF) has allowed for the initiation of comprehensive preclinical animal studies and the initiation of human clinical trials. Results from recent preclinical studies indicated no safety findings which would preclude the chronic administration of rhNGF in clinical trials in humans. Initial Phase I clinical studies in humans indicated that rhNGF produced mild to moderate myalgias shortly following single intravenous or subcutaneous doses of 1 microgram/kg; in general, these effects were not observed at lower doses following single- or multiple-dosing. In addition, following multiple dosing some peripheral neuropathic patients reported an improvement in clinical symptoms which in some cases correlated with improvements in neurological examinations. Future blinded clinical trials should provide important data relevant to the potential therapeutic use of rhNGF.