During infections, the presence of lymphocyte apoptosis both in peripheral blood and in lymphatic organs has been described. This kind of programmed cell death can be either induced by host control mechanisms aimed at eliminating infected lymphocytes and/or retaining immune system homeostasis, or by the pathogen in order to complete its life cycle, spreading the infection and/or suppressing the immune response. Thus, apoptosis has advantages and disadvantages for the host depending on the pathogen life cycle and/or the specificity of the lymphocyte population affected. Identification of the mechanisms involved in autoreactive or pathogen-specific lymphocyte apoptosis could lead to strategies designed to interfere immunologically or pharmacologically in favor of the host.