Carpal tunnel syndrome (CTS) is a constellation of symptoms associated with compression of the median nerve at the wrist. The pathophysiology of CTS is not fully understood but mechanical aspects of injury within the carpal tunnel are most likely. The issues of ischemia, mechanical trauma, ectopic impulse generation, demyelination, tendonitis, elevated carpal tunnel pressure, mechanical factors, small and large fiber involvement and the variability of symptoms are presented. Documentation of neurophysiologic abnormalities in the median nerve is helpful to establish the diagnosis for CTS. There are several types of clinical neurophysiologic evaluations of the median nerve across the wrist. Sensory and motor nerve conduction studies (NCS) of the median nerve segment across the wrist compared to another nerve segment that does not go through the carpal tunnel (i.e. median, radial, or ulnar) are the most sensitive and accurate techniques. Other neurophysiologic techniques used to document CTS include vibrometry threshold testing, current perception testing, Semmes-Weinstein monofilament testing and two-point discrimination. These techniques have considerable subjective components and have not been found to be as sensitive as traditional NCS.