Anaphylaxis, a multisystem allergic reaction, represents a true medical emergency. Anaphylaxis is characterized by a combination of the following: urticaria, angioedema, distributive shock, and respiratory failure. Most often, the patient is rapidly treated with prompt resolution of the anaphylaxis in either the out-of-hospital or emergency department (ED) setting. Infrequently, recurrent, or multiphasic, anaphylaxis is encountered, involving a reappearance of allergic phenomena after complete resolution of the original reaction. Recurrence may involve nuisance-level issues such as urticaria; alternatively, multiphasic reactions may be characterized by cardiovascular collapse and/or respiratory compromise. Initially aggressive pharmacological therapy followed by prolonged observation in either the ED or the in-hospital setting is strongly recommended to monitor for potential recurrence.