Metabolic syndrome affects approximately 44% of the US population over the age of 50 years. Although conflicting definitions exist, the syndrome is typically characterized by abdominal obesity, dyslipidemia, hypertension, and insulin resistance. Thus, it is a major risk factor for both coronary heart disease and type 2 diabetes. Furthermore, the risk of cardiovascular (CV) death is significantly increased in patients with diabetes and/or the metabolic syndrome. Although very few studies exist in patients with the metabolic syndrome, lifestyle changes and drug intervention targeted at the individual components have been shown to reduce the risk of developing diabetes and the incidence of CV disease in high-risk patients. Because many of the conventional antihypertensive drugs may affect the development of new onset diabetes, both positively and negatively, the choice of therapy is particularly important in this population. However, the long-term clinical trials to date have either not included new onset diabetes as a protocol end point or used various different criteria, making comparisons difficult. This review assesses the need for future research into metabolic syndrome and discusses whether clinical surrogates for CV end points, such as new onset diabetes, should be included in clinical trials of new drugs, new regimens, or new indications.