The risk for cardiovascular disease (CVD) is multifactorial and includes such risk factors as diabetes, hypertension, smoking, and dyslipidemia. Thus, targeting the hyperglycemia in type 2 diabetes mellitus (DM) alone will not eliminate all of the excess cardiovascular risk; rather aggressive treatment is needed for all of the modifiable cardiometabolic risk factors. Therapeutic lifestyle change is considered primary therapy for hyperglycemia in type 2 DM. Currently, however, the focus in treatment is on preventing CVD rather than controlling glucose, lipid, or blood pressure (BP) levels. The American Diabetes Association guidelines identify low-density lipoprotein cholesterol as the first priority of lipid lowering, with optimal level set at <100 mg/dL (2.6 mmol/L). To reach the target BP level of <130/85 mm Hg, >65% of patients with DM and hypertension will require 2 or more different antihypertensive drugs. Strategies that combine thiazolidinediones and statins may have complementary effects on cardiovascular risk-factor profiles in type 2 DM, in addition to controlling glycemia. Despite the range of treatment options available, therapeutic agents that target new steps in the progression of CVD are needed, as patients with type 2 DM remain at increased risk and many do not achieve therapeutic targets with the drugs available.