This article focuses on the pathogenesis of the gender gap of autoimmune disease. Specifically, the discussion characterizes the role of sex hormones in the immune response and a female predilection for the common diseases seen in daily practice (ie, lupus erythematosus, myasthenia gravis, and other autoimmune diseases). A comparison between the sexes, with respect to autoimmune disease mechanisms, is presented to give oral and maxillofacial surgeons a better insight as to the role of sex and successful surgical treatment outcomes in this population of patients.