While insufficient cell death of activated T cells can result in autoimmune disorders, elimination of too many T cells can lead to immunodeficiency. Therefore, T lymphocyte fate is highly regulated and requires that cells can switch from an apoptosis‐resistant towards an apoptosis‐sensitive state. This switch is tightly controlled by various effector molecules. Basically, two separate pathways control the fate of antigen‐activated T cells: activation‐induced cell death (AICD) and activated T cell autonomous death (ACAD). Autoreactive T lymphocytes are eliminated by restimulation via their T cell receptor (TCR) and undergo AICD involving death receptors (extrinsic pathway). In contrast, ACAD can lead to T cell deletion without TCR restimulation, and is determined by the ratio between anti‐ and pro‐apoptotic Bcl‐2 family members at the mitochondria (intrinsic pathway). While the extrinsic and the intrinsic pathway lead to caspase activation, non‐caspase proteases (e.g., cathepsins) can be released by the lysosomes and might contribute to AICD as well as to ACAD. Activated T cells posses cell death escape mechanisms which are needed for survival of (memory) T cells, but are deleterious for autoimmune disorders or progression of T cell lymphomas.