Activated T cells must be removed by apoptosis at the end of an immune response in order to maintain cellular homeostasis. Although recent attention has focused on the role of CD95 (Fas/APO-1) in the elimination of activated T cells, apoptosis can also be induced by cytokine deprivation. Here, Arne Akbar and Mike Salmon describe how both death pathways interact in activated T cells and are profoundly influenced by different tissue microenvironments.