Anaphylaxis is a severe, life-threatening immunoglobulin E (IgE)-mediated hypersensitivity reaction. The key to successful management of anaphylaxis involves rapid diagnosis, assessment, and early initiation of therapy. Epinephrine is the undisputed initial therapy for anaphylaxis, and its administration should never be delayed. In most cases, additional interventions such as oxygen therapy, fluid resuscitation, β-agonists, antihistamines, and corticosteroids should be strongly considered. Although hospital course must be individualized to meet each patient's needs, a minimum of 4 to 6 hours of observation period after complete symptom resolution may be reasonable to monitor for recurrence of symptoms and biphasic reaction. Before discharge, every patient should receive patient education about anaphylaxis, a prescription for self-injectable epinephrine, and instructions for follow-up care.