Carpal tunnel syndrome (CTS) is a clinical entity characterized by pain, paresthesias, and numbness in the distribution of the median nerve with weakness and atrophy of the thenar muscles in advanced cases. It is universally accepted that CTS is the clinical concomitant of compression of the median nerve as it passes through the carpal canal. It is reported to be the most common of the entrapment neuropathies. Increasing evidence suggests that occupational factors, including forceful use of the hands, repetitive use of the hands, and hand-arm vibration, are etiologic for CTS. When occurring as a result of occupational exposures, the term “work-related carpal tunnel syndrome” is applied. Clinical approaches to the diagnosis and treatment of work-related CTS are described in this paper. Particular attention is paid to the clinical features and pathophysiology of CTS, the epidemiology of work-related CTS, ascertainment of work-relatedness in the clinical setting, treatment including both work and non-work interventions, and control of occupational ergonomic risk factors that may contribute to the illness. Am. J. Ind. Med. 37:62–74, 2000. © 2000 Wiley-Liss, Inc.