Primary antibody deficiencies have variable autoimmune manifestations. Immunodeficiency and autoimmunity seem to be on opposite sides of clinical immune response, but in reality they are frequently related and can coexist. The most common hypogammaglobulinemias are IgA deficiency, X-linked agammaglobulinemia, and common variable immunodeficiency (CVID). The most common autoimmune disorders are autoimmune hematological disease, autoimmune diseases of the gastrointestinal tract, autoimmune endocrine diseases, and autoimmune rheumatic diseases. Autoimmune manifestations in patients with hypogammaglobulinemias are due to dysregulation of the physiological homostatic mechanisms of the immune system. A variety of autoimmune disorders may dominate the clinical picture of primary immunodeficiency so that the underlying immunodeficiency is overlooked. For early detection and appropriate treatment, autoimmune disease should be suspected in patients with immunodeficiency. The basis of treatment for primary immunodeficiencies is immunoglobulin replacement for antibody deficiency syndromes (other than selective IgA deficiency) and the prevention and aggressive treatment of infections.