Major histocompatibility complex (MHC) molecules or human leukocyte antigens (H LA) are the cell surface molecules responsible from antigen presentation and activation of T cells. At the same time MHC molecules determine direction of T cell response. Unlike T cells, antigen specificity of MHC molecules is not high and they can not differenciate self and non-self antigens from each other. MHC molecules are classified as MHC I (HLA-A, B, C) and MHC II (HLA-DP, DR, DQ) molecules which are structurally similar. MHC I molecules present intracellular antigens such as viruses and tumor antigens to CD8+ cytotoxic T cells and MHC II molecules present endocytosed bacterial antigens to CD4+ helper I cells. MHC molecules are encoded by the highly polymorphic genes in a giant locus called MHC. in addition to high polymorphism in MHC genes, they are also charactized by having continuous mutations and codominant expression pattern to increase the diversity among individuals. In evolutionary context, immunologic diversity is important for an uninterrupted life on the Earth. However this diversity causes vast differances among the people in terms of their responses to infections and tendency to have autoimmune and allergic diseases. In this article, structural and functional features of MHC molecules and their common roles in disease formation are discussed.