The primary target in the treatment of hypercholesterolemia is often to lower low-density lipoprotein (LDL) cholesterol, rather than improve clinical outcomes. Despite the wide use of lipid-modifying drugs, considerable cardiovascular mortality and morbidity remains with this disease. Hypercholesterolemia plays a key role in the development and progression of atherosclerosis and can lead to cardiac heart disease. The purpose of this review is to determine whether ezetimibe has proven clinical benefits; it discusses the clinical trials of simvastatin and ezetimibe alone and in combination. Simvastatin has been clearly shown to decrease LDL-cholesterol, which is associated with the slowing of atherosclerosis and a reduction in cardiovascular morbidity and mortality. Ezetimibe alone or in the presence of simvastatin lowers LDL-cholesterol. However, ezetimibe alone or in the presence of simvastatin has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Thus, until/unless the use of ezetimibe is clearly shown to improve clinical outcomes, its use should be largely restricted to clinical trials investigating clinical outcomes and should not be used routinely in everyday practice.