Epinephrine is crucial in the treatment of anaphylaxis. As anaphylaxis frequently occurs in nonmedical settings, use of an epinephrine auto-injector is vital for prompt management. This article provides an overview of the increasing number of epinephrine auto-injector prescriptions and the underlying causes and contributing factors to these rising prescriptions. It also reviews the current indications for prescription of an epinephrine auto-injector, proper use of epinephrine auto-injectors, and the management of unintentional epinephrine injections.