The recognition that hypertension and dyslipidemia coexist more often than would be expected by chance and that their combination increases the risk of coronary heart disease (CHD) has important implications for patient management. Patients with cardiovascular disease (CVD) and healthy individuals with multiple CVD risk factors--including concomitant dyslipidemia and hypertension-are the primary focus of updated treatment guidelines for CVD prevention. There is a need for a treatment paradigm shift from the diagnosis and treatment of individual CVD risk factors to the assessment and management of total CVD risk. Goals for each CVD risk factor need to be intensified when multiple sources of risk are present. Patients who have no overt disease but who have multiple CVD risk factors are now understood to be at high risk and should be the target of aggressive primary preventive strategies to avert unnecessary morbidity and mortality. It is also becoming clear that CVD risk factors interact at the level of the endothelium to promote atherosclerosis. Furthermore, recent clinical trials, including those assessing atherosclerotic progression and CVD endpoints, have demonstrated the effectiveness of interventions targeted at multiple risk factors for CVD.