Activated T-cells are believed to play a critical role in the pathogenesis of autoimmune disease. In experimental allergic encephalomyelitis (EAE), an animal model resembling human multiple sclerosis (MS), there is evidence that T cells reactive to myelin basic protein mediate an inflammatory response within the central nervous system leading to demyelination. Furthermore, encephalitogenic T cells express TCR with highly restricted V gene usage and consequently specific forms of immunotherapy directed against V gene products have been successful in preventing and treating EAE. These findings prompted studies into the analysis of TCR repertoire expression in human autoimmune diseases in an attempt to identify the TCR usage of autoreactive and potentially pathogenic T cells. However, this has proved difficult as the autoantigens that drive the T cell response in most human autoimmune disorders are unknown. This review examines the data that have accumulated over the past few years on TCR usage in human autoimmune diseases and is focused largely on rheumatoid arthritis and MS.