Activation of the T-cell co-receptor cytotoxic T-lymphocyte antigen 4 (CTLA4) has a pivotal role in adjusting the threshold for T-cell activation and in preventing autoimmunity and massive tissue infiltration by T cells. Although many mechanistic models have been postulated, no single model has yet accounted for its overall function. In this Opinion article, I outline the strengths and weaknesses of the current models, and present a new 'reverse stop-signal model' to account for CTLA4 function.