Currently, a plethora of antihypertensive medications exists. One concern about the long‐term use of many of these agents is that adverse effects may offset their benefits. Despite the availability of many newer agents, blood pressure continues to be inadequately controlled in the majority of treated hypertensive patients, and many still remain at higher risk of premature death than the general population. More than 60% of treated hypertensive patients fail to attain blood pressures of < 140/90 mmHg. The major factors that permit a rational choice of medication include demographic considerations such as race and age, coexisting diseases, safety, patient acceptance (quality of life), potential drug interactions, and additional salutary effects. The role of nondiuretic monotherapy is an integral component of this discussion. Preliminary data indicate that the use of calcium‐channel blockers, converting‐enzyme inhibitors, and All‐receptor antagonists constitutes excellent therapy in many patients. The effects of medication on the metabolic and lipid profiles are also considered.