Mutations in genes expressed in Schwann cells and the axons they ensheathe cause the hereditary motor and sensory neuropathies also known as Charcot-Marie-Tooth disease (CMT). More than 33 different genes have been shown to cause inherited neuropathies. Chromosomal localization of many other distinct inherited neuropathies has been mapped, and new genetic causes for inherited neuropathies continue to be discovered. How to keep track of all of these disorders, when to decide to pursue genetic testing, and what tests to order for specific patients are difficult challenges for any neurologist. In this review, these issues are addressed and illustrative cases are provided to help in dealing with them. CMT can serve as a living microarray system to identify molecules necessary for normal peripheral nervous system (PNS) function. When investigators understand how these various molecules interact, the pathogenesis of peripheral neuropathies in general, as well as of other neurodegenerative disorders involving the PNS, will be better understood.