Recent trials of patients with cardiovascular disease (CVD) have provided a wealth of data regarding diagnosis, risk factors, and treatment. Aggressive risk factor management has been shown to improve patient survival, reduce recurrent events and the need for interventional procedures, and improve the quality of life in patients with known CVD. There have been impressive reductions in blood pressure and low-density lipoprotein cholesterol levels, and improved diabetes control. Medical therapy with options such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin has been shown to have positive effects. Patients in current trials are more likely to be receiving appropriate treatment upon study entry than were patients in older trials. Changes in the risk profile of high-risk patients have reduced the overall rates of cardiovascular events and will continue to affect outcomes in randomized clinical trials. Such changes should be considered in the design of new clinical trials and in the interpretation of current data.