Recent clinical trials have demonstrated that reductions of serum low-density lipoprotein (LDL) levels substantially decrease the risk for coronary heart disease. These trials confirm other lines of evidence that high levels of LDL are a critical atherogenic factor. Aggressive lowering of LDL levels in high-risk patients promises to significantly reduce morbidity and mortality from coronary heart disease in the first third of the 21st century. However, several additional measures will be required to marginalize coronary heart disease in the 21st century. Other lipoprotein abnormalities and other risk factors, eg, cigarette smoking, hypertension, and diabetes mellitus, must be controlled to obtain the full benefit of LDL-lowering therapy. Moreover, the health care delivery system must be reorganized to put more emphasis on prevention. Although much can be achieved through application of current knowledge in prevention efforts, further advances through new research will be required to remove coronary heart disease as a major cause of death in the United States.