Classic forms of hereditary angioedema are characterized clinically by recurrent episodes of angioedema, biochemically by reduced C1 inhibitor level and/or function, and genetically by a heterogeneous group of mutations in the C1 inhibitor gene that have an autosomal dominant mode of transmission. Androgens and estrogens have significant clinical effects in patients with hereditary angioedema, and tend to have antagonist effects of the levels of C1 inhibitor protein. Androgens increase the levels of C1 inhibitor protein, reduce attacks of angioedema, and thus are an important therapy for patients. The mechanisms by which the sex steroid hormones achieve these effects are not understood. The recent recognition of a novel estrogen-dependent form of angioedema may offer important insights into the mechanisms by which the sex hormones exert their effects, and the pathogenesis and treatment of both estrogen-dependent and classic forms of hereditary angioedema.