Although hereditary angioedema accounts for only a small fraction of all cases of angioedema, it is the most common genetically linked clinical disorder caused by the deficiency of a protein associated with complement activation. Attacks may be complicated by incapacitating cutaneous swelling, life-threatening upper airway impediment, and severe gastrointestinal colic. Recent physicochemical and genetic studies have contributed significantly to our understanding of the structure of the inhibitor protein. Measurement of serum C4 titer is an efficacious screening test. Normal levels during symptomatic periods rule out the diagnosis, whereas decreased levels warrant determination of C1 esterase inhibitor titer by immunoassay or functional assay. The functional assay is necessary to ascertain the genetic variant form. The importance of making the correct diagnosis cannot be overemphasized. It can avert potentially fatal consequences, such as upper airway obstruction and unnecessary abdominal surgery. The application of short-term preventive measures can avoid complications associated with trauma. Finally, abatement or elimination of symptoms in patients with incessant and disabling attacks can be attained by long-term therapy with currently available attenuated androgens.