Anaphylaxis is the quintessential critical illness in emergency medicine. Symptoms are rapid in onset and death can occur within minutes. Approximately 1500 patients die annually in the United States from this deadly disorder. It is imperative, therefore, that emergency care providers be able to diagnose and appropriately treat patients with anaphylaxis. Any delays in recognition or initiation of therapy can result in unnecessary increases in patient morbidity and mortality.Recent literature, including updated international anaphylaxis guidelines, has improved our understanding and management of this critical illness. Anaphylaxis is a multisystem disorder that can manifest signs and symptoms related to the cutaneous, respiratory, cardiovascular, and gastrointestinal systems. Epinephrine remains the drug of choice and should initially be administered intramuscularly, into the anterolateral thigh, as soon as the diagnosis is suspected. For patients unresponsive to repeated intramuscular injections, a continuous infusion of epinephrine should be started. Antihistamines and corticosteroids are second-line medications and should never be given in lieu of, or prior to, epinephrine. Aggressive fluid resuscitation should also be used to treat the intravascular volume depletion characteristic of anaphylaxis. Patient observation and disposition should be individualized, as there is no well-defined period of observation after resolution of signs and symptoms.For patients with anaphylaxis, rapid and appropriate administration of epinephrine is critical for survival. Additional therapy, such as supplemental oxygen, intravenous fluids, antihistamines, and corticosteroids should not delay the administration of epinephrine.