One major problem in the management of hypertensive patients is their lack of compliance with therapeutic regimens. Some of the problem with compliance is due to side effects of the drugs being used. Additionally, drug resistance may be related to interactions of antihypertensive drugs with other prescription and nonprescription drugs. By classifying drugs into common modes of action, common side effects can be predicted. However, each drug has its own spectrum of other side effects which can be dose-limiting. Most of the side effects are extensions of the pharmacologic actions of these drugs, and only relatively rarely is an allergic reaction a problem. Drug interactions can be important in explaining some side effects or drug resistance. A knowledge of the pharmacology of the antihypertensive drugs allows the physician to predict, in many cases, the possibility of an interaction and, indeed, can allow the use of interactions to advantage as with combinations of vasodilators and beta adrenergic blocking drugs. Until such time as the perfect antihypertensive drug is discovered, most patients can be managed satisfactorily with minimal side effects by judicious combination of available drugs and avoiding drugs which interact to cause more side effects or decrease the antihypertensive effects.