The scope of expenditures due to anaphylaxis likely is underestimated by health care payors because anaphylaxis is underdiagnosed and, when reported, most costs of anaphylaxis borne by payors relate to direct medical expenses. Direct costs of anaphylaxis have been estimated at $1.2 billion per year, with direct expenditures of $294 million for epinephrine, and indirect costs of $609 million. More accurate diagnostic coding will allow payors to improve their understanding of the full impact of anaphylaxis on health care plans, employers, patients, and their families. Similarly, more accurate diagnosis and treatment of anaphylaxis should have a direct effect on overall cost savings achieved in this disease state. This includes savings in both direct costs, such as emergency department visits, and indirect costs, such as lost productivity of patients and caregivers. Educating medical personnel on treatment guidelines regarding the specific use of appropriate epinephrine autoinjectors will contribute to cost savings. Even though the cost of autoinjectors has been increasing, evidence indicates that the cost of improper response to, and treatment of, anaphylaxis outweighs that increase. At this time, there are several branded epinephrine autoinjectors and one generic equivalent for one of these branded products available on the US market; the branded autoinjectors are not considered equivalents for substitution. Barriers to coverage and access, such as managed care organization tier classification, medication copay, and socioeconomic status of specific patients, need to be examined more closely and addressed. Education in the proper use of epinephrine autoinjectors, including regular checking of medication expiration dates, is critical for proper management of anaphylaxis and minimizing the costs of anaphylactic events. Managed care organizations can play a role in educational initiatives.