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Summary: Cardiovascular disease (CVD) is the leading cause of death and disability in industrialized societies, due in large part to the lack of a comprehensive approach to control the risk factors for atherosclerosis. One strategy for reducing an individual's global CVD risk relies on a targeted approach that modifies each of the major independent risk factors prevalent in both symptomatic (secondary prevention) and asymptomatic (primary prevention) patients. These interventions include lipid lowering, smoking cessation, blood pressure control, glycemic control, regular exercise, and the use of various medications. This review offers an evidence-based strategy toward reducing an individual's global risk for CVD by addressing the modifiable, major independent risk factors.