Unstable angina can be defined by the development of chest pain at rest, usually with reversible S-T segment changes. It has been found in patients in whom angina developed at rest in the cardiac catheterization laboratory that a decrease in coronary sinus oxygen saturation preceded changes in left ventricular relaxation and contractility that preceded the development of chest pain and/or electrocardiographic changes. Increases in heart rate and/or blood pressure followed, rather than preceded, these ischemic episodes. These findings suggest that a decrease in oxygen supply, rather than an increase in oxygen demand, is the cause of episodes of angina at rest. Although principles of treatment of effort angina have emphasized the reduction of myocardial oxygen demand, treatment of rest angina should logically emphasize therapies that improve oxygen supply. A stepwise approach to the treatment of patients admitted to the Coronary Care Unit with unstable angina is proposed. The initial step consists of replacing oral and/or transcutaneous nitrates with an intravenous infusion of nitroglycerin while maintaining beta-blockers and calcium blockers at their previous doses. Nitroglycerin dilates coronary arteries and intercoronary collateral channels in addition to reducing preload and afterload. Intravenous administration allows faster titration to an effective dose and also more rapid reversal of hemodynamic effects, if the patient's status changes. The second step would consist of maintaining the nitroglycerin infusion and beta-blockers and adding or increasing the dose of calcium channel blockers. Slow channel calcium blockers dilate coronary arteries and prevent or reverse coronary spasm in addition to reducing afterload. The third step consists of adding or increasing the dose of beta-blockers in subgroups of patients with resting tachycardia and/or arterial hypertension. The fourth and final step would be to employ intra-aortic balloon counterpulsation therapy and/or to perform urgent coronary angiography. In patients with suitable coronary anatomy, angiography could be followed by percutaneous transluminal angioplasty or coronary artery bypass surgery.