Peripheral neuropathy is a common dose-limiting toxicity of chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) causes numerous debilitating symptoms, impairs functional capacity, and results in dose reductions or possible cessation of chemotherapy. Analgesic or neurotropic agents are only modestly effective in treating neuropathic symptoms. Animal and human studies into the pathogenesis of CIPN have demonstrated heterogeneity in the mechanism(s) of nerve injury caused by individual agents, which may partly explain the wide variation in the resultant symptoms. Development of optimal therapeutic measures to treat CIPN requires continued research into the pathophysiologic basis of nerve injury, identification of risk factors for individual patients, development of reproducible and easy-to-use measurement scales, and finally, the performance of appropriately designed clinical trials to evaluate potentially promising agents.