&NA;Complete deficiency of one of the early components (C1, C4, or C2) of the classical pathway of the complement cascade is one of the strongest genetic risk factors for systemic lupus erythematosus that has been recognized. The lupus that occurs in complement‐deficient individuals typically presents in early childhood. The association of complement deficiency and lupus has been known for over two decades, yet the explanation remains somewhat elusive. Complement component deficiencies may be associated with other rheumatic or autoimmune disorders and both partial and acquired complement component deficiencies are also associated with an increased risk of autoimmune disease. This article reviews the current understanding of the relationship between complement component deficiencies and autoimmunity. Recent data from animal models and new types of genetic analyses are reviewed.