The autoimmune diseases result from inappropriate responses of the immune system to self antigens. The etiology of autoimmune diseases remains largely unknown but candidate etiologic factors include genetic abnormalities and infections. Although there are considerable data supporting the role of infections in a variety of autoimmune diseases, this role has been unequivocally established in only a few autoimmune diseases. The difficulty in establishing the infectious etiology of autoimmune diseases stems from several factors such as the heterogeneity of clinical manifestations in individual autoimmune diseases and the time interval between infection and autoimmune disease. The data on this association derive from clinical observations, epidemiological studies and research using laboratory techniques, protein sequence database screening and animal models. Infectious agents can cause autoimmune diseases by different mechanisms, which fall into two categories: antigen specific in which pathogen products or elements have a central role e.g. superantigens or epitope (molecular) mimicry, and antigen non-specific in which the pathogen provides the appropriate inflammatory setting for “bystander activation”. The most important mechanisms are molecular mimicry and superantigens. As far as molecular mimicry is concerned the recent data on the degeneracy of T cell recognition shifted the focus from searching for linear sequence homology to looking for similarity of antigenic surfaces. Special mention has to be made to retroviruses as they have some unique means of inducing autoimmunity.