Apoptosis is a programmed cell death that represents a normal component of the development, differentiation and health of multicellular organisms leading to an adequate cellular turnover and homeostasis. In autoimmune diseases, the immune system recognizes various autoantigens causing damage in target organs. Dead cells represent an important source of autoantigens that, in particular conditions, can represent a stimulus for an autoimmune response. A large number of studies reported the impairment of the apoptosis regulatory mechanisms in immune cells as a pivotal element in the pathogenesis and evolution of autoimmune disorders. Several pathogenetic pathways have been claimed to account for autoimmunity development during apoptotic processes. In fact, interestingly abnormalities potentially leading to immune disorders have been described as occurring in each step involved in apoptosis, from the very beginning to the post death phenomena. In this extent we propose a systematic review of the molecular mechanisms strictly leading to apoptosis with particular interest to their alterations, potentially causing tissue specific and/or systemic autoimmunity.