During ageing the immune system is characterized by a peculiar remodelling, called immunosenescence. Apoptosis or programmed cell death plays a central role in this process. Both recurrent antigenic stimulations and oxidative metabolism byproducts, impinging upon the immune system, modify the apoptotic capability of lymphocytes, driving immunosenescence. The cells of the immune system undergo two different kinds of apoptotic processes: activation-induced cell death (AICD), peculiar to immune cells and geared towards the elimination of unnecessary lymphocytes following clonal expansion, and damage-induced cell death (DICD),a more generalized phenomenon in response to a variety of cellular insults, mainly oxidative metabolism by-products, particularly important for preventing the onset of neoplastic proliferations. The subtle remodelling of both these apoptotic pathways in the elderly contributes to the phenotypic and functional characteristics of the aged immune system and in addition to the upregulation of anti-stress responses and inflammatory cytokines (inflammageing), represents one of the major determinants of ageing rate and longevity, as well as of the most common age-related diseases. A correct modulation of apoptosis in specific lymphocyte subsets could preserve immune function in the elderly and may be useful for prolonging the lifespan and reducing age-related degenerative, inflammatory and neoplastic diseases, contributing to successful ageing.