Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder that usual results from a decreased level of functional C1-INH and clinically manifests with intermittent attacks of swelling of the subcutaneous tissue or submucosal layers of the respiratory or gastrointestinal tracts. Laboratory studies and radiographic imaging have limited roles in evaluation of patients with acute attacks of HAE except when the diagnosis is uncertain and other processes must be ruled out. Treatment begins with assessment of the airway to determine the need for immediate intervention. Emergency physicians should understand the pathophysiology of HAE to help guide management decisions.