Hereditary Angioedema (HAE) is a multisystem, autosomal dominant disease that affects ~1:10,000 to 1:50,000 individuals in the United States. The disease has several clinical characteristics that distinguish it from other forms of angioedema. Recurrent swelling attacks involve the abdomen, face, extremities, genitalia, oropharynx, or larynx without urticaria. The swelling attacks are typically unilateral, nonpitting, nonpruritic, and, although uncomfortable, are often painless. Other forms of isolated angioedema such as acquired angioedema and angiotensin-converting enzyme-induced angioedema have similar characteristics of HAE. Therefore, evaluation of patients with recurrent angioedema should be directed at excluding these different forms of angioedema before a diagnosis of idiopathic angioedema is made. The objective of this article is to provide an overview of the differential diagnosis of angioedema that reflects the angioedema guidelines that are currently in development.