Underlying medical illness and drug interactions may make the use of psychotropic agents in some physically ill patients problematic. This overview, published in two parts, discusses six major classes of psychotropic medications (cyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, neuroleptics, lithium, psychostimulants, and carbamazepine) and examines their use in the setting of specific types of medical illnesses (e.g., cardiovascular, pulmonary, hepatic, and renal disease). Practical considerations in using psychotropic medications in medical-surgical patients, particularly those who are elderly or medically debilitated, receive special emphasis. In part I, the use of cyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, and buspirone are discussed.