There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization’s Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.