T cell activation is brought about by recognition of peptide/MHC complexes on an antigen-presenting cell (APC) by the T cell receptor (TCR). However, in general this appears to be insufficient for the full development of T cell responses and therefore additional signals are required, provided by ligation of counter-receptors on the T cell by APC accessory molecules. Although many studies have suggested that B7 molecules (CD80/CD86) binding to CD28 induce this second signal, it is now evident that any one of a number of molecules may provide accessory function and that efficient response is only generated following multiple interactions. It has also become clear that T cells exist in varying states of activation or differentiation, and that requirements for accessory molecules and costimuli are not always equivalent. This review covers much of the recent data regarding accessory molecule regulation of T cell responses. A modified version of the two signal model is presented, suggesting that the major function of accessory molecules during the initial stages of activation is to augment the ability to signal through the TCR, and that the primary role of costimulatory signals is to allow IL-2 secretion and growth. The requirement for multiple accessory molecules interactions is discussed in relation to activation of naive T cells and how such interactions are less critical at the memory and effector stages. Finally, this new information is related to how T cells interact with varying APC and how these interactions may modulate T cell response.