Activation-induced apoptosis has been proposed as a mechanism for purging the immune repertoire of anti-self specificities, not only in development but also during the generation of somatic mutation in germinal centers. The pathways involved in driving immature and mature T and B cells to programmed cell death are reviewed with respect to two hypotheses, the pre-emptive death model, in which certain signals are obligatory for programmed cell death, and the two signal: death/survival model. Depending on the system, some data support the former pathway, in which certain signals are obligatory for programmed cell death, whereas other data are consistent with the two signal hypothesis. Moreover, recent data suggests that the c-myc protein plays a pivotal role in controlling this process. Finally conflicting roles of protein kinases, bcl-2 and p53 are reviewed and contrasted for involvement in activation-induced cell death in T and B lymphocytes.