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Epinephrine is a life-saving medication in the treatment of anaphylaxis, in which it has multiple beneficial pharmacologic effects. Here, we examine the evidence base for its primary role in the treatment of anaphylaxis episodes in community settings.We review the practical pharmacology of epinephrine in anaphylaxis, its intrinsic limitations, and the pros and cons of different routes of administration. We provide a new perspective on the adverse effects of epinephrine, including its cardiac effects. We describe the evidence base for the use of epinephrine in anaphylaxis. We discuss the role of epinephrine auto-injectors for treatment of anaphylaxis in community settings, including identification of patients who need an auto-injector prescription, current use of auto-injectors, and advances in auto-injector design. We list reasons why physicians fail to prescribe epinephrine auto-injectors for patients with anaphylaxis, and reasons why patients fail to self-inject epinephrine in anaphylaxis. We emphasize the primary role of epinephrine in the context of emergency preparedness for anaphylaxis in the community.Epinephrine is the medication of choice in the first-aid treatment of anaphylaxis in the community. For ethical reasons, it is not possible to conduct randomized, placebo-controlled trials of epinephrine in anaphylaxis; however, continued efforts are needed towards improving the evidence base for epinephrine injection in this potentially fatal disease.