Anaphylaxis is a severe life-threatening systemic reaction that otolaryngologists may come in contact with through emergency cases, or in their offices when delivering allergy immunotherapy. Rapid recognition of the entity should be followed by epinephrine administration. Anaphylaxis causes, including a hypothetical scenario, are described. Various risk factors for anaphylaxis, such as β-blocker use, are discussed. The differential diagnosis of anaphylaxis and adjunct treatment are explained.