Anaphylaxis associated with insect stings has been reported to cause approximately 40 deaths per year in the United States. Immunotherapy with venom extracts is a well-established method of treatment of allergy to insect stings. The duration of therapy is based mainly on the initial symptoms and the presence or absence of systemic symptoms during therapy. Evaluation of immunoglobulin E and immunoglobulin G levels as well as repeat skin tests and sting challenges may also provide some additional benefit but are not as useful as the former two criteria. Patients with mastocytosis have a particularly increased risk for anaphylaxis after insect stings. There are many case reports of individuals first diagnosed with mastocytosis after an episode of anaphylaxis after an insect sting, in addition these patients tend to have more severe reactions as well as repeated episodes of systemic reactions during immunotherapy. Early diagnosis of mastocytosis and proper treatment can contribute greatly to the outcome in patients who present with venom allergy.