Cell death by apoptosis plays a significant and seemingly contradictory role in the development and pathogenesis of autoimmune diseases. Apoptosis is integral to the assembly and maintenance of a healthy, self-tolerant immune system. However, many of the molecular and cellular events specific to apoptosis generate a reservoir of self-antigens with the potential to initiate and possibly perpetuate autoimmune conditions. Recent findings that support this latter, more sinister role for apoptosis have shed light on a mystery that is common to many systemic autoimmune diseases, namely, why the majority of autoantibodies produced in patients with these diseases target proteins that are normally found inside the cell, often within the nucleus. This review will discuss how autoantigens are specifically altered during the apoptotic process, and how the complement system participates in recognizing and clearing these potentially immunogenic packages.