Approximately 1 to 3% of the general population has had a systemic reaction to insect stings. Adults whose reactions include urticaria, obstruction of the upper or lower airway, or hypotension and children whose reactions include obstruction of the upper or lower airway or hypotension have an increased risk of future systemic reactions to stings. Allergy skin tests to Hymenoptera venoms can help to identify the offending insect and to classify the reactions as allergic; however, because 15% of the general population may have positive results to such tests, persons who have not experienced a systemic reaction to insect stings should not be tested. Venom immunotherapy is highly effective and confers 98 to 99% protection in patients who have experienced previous systemic reactions to insect stings. Reaction rates to venom skin tests or venom immunotherapy are low and are similar to those in allergy testing and immunotherapy for hay fever. Generally, patients who have had systemic reactions to stings should be assessed by an allergist to determine whether they are candidates for immunotherapy with Hymenoptera venom. The decision to institute venom immunotherapy should be based on the disposition of the patient, the severity of the reaction, and the risk of subsequent stings. Deliberate sting challenges are clinically useful for guiding immunotherapy.