CD4 and CD8 are cell-surface glycoproteins that participate in molecular complexes involved in both T cell development and antigen recognition by T cells. CD4 and CD8 interact with nonpolymorphic regions of class II and class I major histocompatibility complex (MHC) molecules, respectively, and these interactions result in increased intercellular adhesion and enhanced stimulation of T cells. A src-like tyrosine kinase, p56lck, is associated with the cytoplasmic domain of both CD4 and CD8 and may be involved in transmembrane signaling. Crystal structures of extracellular regions of CD4 and CD8 have been determined and have provided a basis for understanding and probing CD4 and CD8 function. The structures of CD4 and CD8 are reviewed here, along with the implications of these structures for CD4 and CD8 function.