Many autoimmune diseases are characterized by generation of autoantibodies that bind to host proteins or deposit within tissues as a component of immune complexes. The autoantibodies can activate the complement system, which can mediate tissue damage and trigger systemic inflammation. Complement inhibitory drugs may, therefore, be beneficial across a large number of different autoimmune diseases. Many new anti-complement drugs that target specific activation mechanisms or downstream activation fragments are in development. Based on the shared pathophysiology of autoimmune diseases, some of these complement inhibitory drugs may provide benefit across multiple different diseases. In some antibody-mediated autoimmune diseases, however, unique features of the autoantibodies, the target antigens, or the affected tissues may make it advantageous to block individual components or pathways of the complement system. This paper reviews the evidence that complement is involved in various autoimmune diseases, as well as the studies that have examined whether or not complement inhibitors are effective for treating these diseases.