Treatment of hypertension in the complicated patient requires a specialized approach focusing on the treatment of the blood pressure and concurrent medical problems. Therapy must be chosen in consideration of the patient's age, multiple illnesses, declining organ function, and possible drug interactions. This requires that the antihypertensive agent chosen have a demonstrated safe profile. In clinical trials, monotherapy with the calcium channel blocker (CCB) isradipine (ISR) at a recommended therapeutic dosage has controlled blood pressure with an excellent level of safety. In these studies, ISR had no significant effect on heart rate, cardiac conduction, or cardiac contractility and no negative effect on renal function. In hypertensive patients with both normal and impaired renal function, ISR significantly increased renal plasma flow while decreasing renal vascular resistance without decreasing glomerular filtration rate and filtration fraction. ISR has long-term natriuretic effects that may provide additional benefits in antihypertensive therapy. Most adverse effects associated with ISR are mild, transient, and related to vasodilation. The most frequently reported adverse reactions are headache, dizziness, and edema. ISR does not affect glycemic control or lipid metabolism in either diabetic or nondiabetic patients. It has no reported adverse interaction with some of the most commonly used medications for elderly patients, including digoxin, nitroglycerin, oral hypoglycemics, and hydrochlorothiazide. ISR may be used as a first-line agent for the treatment of hypertension in complicated patients.