Apoptosis is important far maintaining peripheral lymphocyte homeostasis and for minimizing the accumulation of autoreactive lymphocytes. Disruption of apoptotic pathways has been linked to lymphadenopathy, breakdown of peripheral tolerance and the development of autoimmune diseases. Major progress has been made during the past year in understanding the critical roles of a variety of signaling molecules, especially a group of cysteine proteases, for the execution of apoptosis. These proteases appear to be the primary effector molecules responsible for carrying out lymphocyte apoptosis and may be critical for peripheral immunological tolerance.