Histamine release and adverse pseudoallergic/allergic reactions during the perioperative period occur frequently. The incidence of such reactions is 20%-30% for all grades of severity, 1%-5% for systemic reactions, and 0.1%-0.5% for life-threatening reactions. They can be elicited by all commonly used anesthetic agents and by surgical interventions. Both the incidence and severity can be reduced by the use of combined prophylaxis with H1- + H2-receptor antagonists. The authors recommend that this prophylaxis be given to the following groups of patients: those with a history of adverse reactions or history of allergy, patients undergoing surgery with a high risk of histamine release, elderly patients, and those with poor physical status due to underlying systemic diseases. These indications have been developed by heuristic medical decision-making, including a decision tree.