Hereditary angioedema (HAE) is a relatively rare genetic disorder that is usually characterized by either low levels of C1 esterase inhibitor (C1-INH) or the presence of dysfunctional C1-INH. It can present with relatively mild and self-limiting symptoms, but it is also potentially fatal; the most common cause of death is asphyxiation secondary to edema of the upper airway. The diagnosis of HAE, especially in the emergency situation, is not straightforward. HAE must be distinguished from several other types of angioedema that require different management approaches. Management approaches include trigger avoidance and pharmacologic therapy; the latter has traditionally involved the administration of attenuated androgens and antifibrinolytics. Recently, a new class of agent-C1-INH-has been introduced in the United States. This article provides an update on the pathophysiology, clinical picture, diagnosis, prophylaxis, and acute treatment of HAE. We must keep HAE in mind as a possible diagnosis whenever we are faced with a case of unexplained angioedema if we are to take advantage of the effective and more specific therapies that are becoming available.