Demyelinating neuropathies are disorders of the peripheral nervous system in which the myelin sheath of axons is affected by immune-mediated or genetically determined processes. In single axons, demyelination yields conduction block due to extinction of action potentials or conduction slowing. Motor nerve conduction studies assess these phenomena in nerves, which consist of many axons. It is important to distinguish demyelinating from axonal polyneuropathies as this allows accurate diagnosis and institution of appropriate treatment. Immunological treatment in acquired demyelinating polyneuropathies is often successful. Criteria were developed for motor conduction velocity slowing and for conduction block, which assume demyelination if the findings cannot be explained by axon loss. Criteria-sets for the diagnosis of specific polyneuropathies require that several variables are consistent with demyelination in several nerves. However, these sets are based on expert opinion and have a low sensitivity such that treatable neuropathies may be underdiagnosed. Evidence-based sets are currently being developed. Axon loss is the main determinant of the clinical deficit in demyelinating neuropathies and, if its mechanisms are further elucidated, it may be prevented by pharmacological treatment. Excitability testing, which assesses axonal membrane potential and ion-channel activities, may reveal some of these mechanisms.