Anaphylaxis is a severe life-threatening systemic reaction that offers many challenges to the clinician. The incidence of anaphylaxis is significant in the general population and an important cause of morbidity and mortality. While the most common causes of anaphylaxis include drugs, foods, and venoms, other important etiologies must be considered. The etiology of anaphylaxis is classically based on IgE mediated hypersensitivity but multiple mechanisms may be involved. The clinical presentation of anaphylaxis may be extremely variable with a broad differential diagnosis which will be outlined. Although the diagnosis of anaphylaxis can many times be based on a careful history and physical examination, there are laboratory and skin tests which may be helpful in establishing a diagnosis in some cases. The cornerstone of treatment of anaphylaxis remains epinephrine. Other supportive therapies will be discussed.