It has been customary to consider that antigen-presenting cells provide, in addition to the presented antigen, a second or co-stimulatory signal that leads to T-cell growth and effector function. The recent literature indicates that this two-signal notion oversimplifies the function of antigen-presenting cells. Instead it is useful to consider four groups of events: the formation of peptide-MHC complexes, the role of soluble cytokines, the action of antigen-presenting cell-T cell molecular couples distinct from the receptor for peptide MHC, and the function of antigen-presenting cells in situ.