Immunity to both extracellular and intracellular pathogens is achieved in part when T lymphocytes recognize foreign antigen in the context of antigenpresenting molecules. Antigen recognition by T cells occurs via binding of the T-cell receptor (TCR) to MHC class I, class II, or CD1 molecules. Extracellular bacterial or parasitic challenges to the immune system are mediated in part by antibody recognition of extracellular antigens. Antibodies are produced by B lymphocytes, which require the help of activated antigen-specific CD4+ T cells to proliferate and secrete highaffinity antibodies. Viruses, and some bacterial pathogens and parasites, replicate within host cells, where they cannot be detected by antibodies. The destruction of virus-infected cells is the task of cytotoxic T lymphocytes that possess T-cell receptors specific for viral peptides presented in the context of MHC class I molecules. This review will focus on the three modes of antigen presentation to T cells and the cell biological aspects of assembly and trafficking of the molecules involved.