Autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, affect approximately 4% of the population in industrialized countries, and are characterized by an immune-mediated destruction of autologous cells and/or tissues. More knowledge is needed to prevent and treat this large group of diseases. Unravelling the genetic predisposing factors is important in this respect, and large research efforts have been initiated to reach this goal. The human MHC, also called the human leukocyte antigen (HLA) complex, is known to harbour major genetic determinants for autoimmune diseases. For several autoimmune diseases certain classical HLA class II and/or class I genes are strongly associated with disease. As a result of recent systematic screening studies additional genes and regions in the MHC, including the extended MHC, are now known to contribute to the predisposition.