Apoptosis is a physiological process of cell death that normally occurs when cells are damaged or no longer needed. One of its major roles is the maintenance of peripheral immune tolerance, by eliminating activated T and B cells beyond the course of an infection, and thus terminating immune responses. When apoptosis becomes dysfunctional, either being "too much" or "too little," a variety of different disease states may be triggered. For example, insufficient apoptosis of activated immune cells is the basis of the Canale Smith Syndrome /ALPS, whereas excessive apoptosis of ~ islet cells of the pancreas is involved in the pathogenesis of autoimmune diabetes mellitus. In this review, we explain the fundamental aspects and molecular mechanisms of apoptosis and their relevance to several important human autoimmune diseases.