Coronary artery disease (CAD) is still a major cause of mortality in developed countries, and dyslipidemia is one of its major causes. In an attempt to reduce both mortality and morbidity from CAD, several dietary, pharmacological, and surgical approaches have been used to reduce plasma cholesterol levels. In this brief review, we summarize the evidence for cholesterol-lowering effects and safety of partial ileal bypass (PIB) procedure in both human and animal studies. The results of the Program on the Surgical Control of the Hyperlipidemias (POSCH), which involved a total of 838 subjects with myocardial infarction, are promising. A 5-year follow-up of this study revealed significant reductions of up to 27% in total cholesterol (TC) and up to 42% in low-density lipoprotein (LDL) cholesterol levels along with an increase of up to 8% in high-density lipoprotein (HDL) cholesterol levels as compared to controls. These changes were associated with other benefits such as increased HDL/TC and HDL/LDL ratios, and a significant decrease in apolipoprotein (apo) B100 and increase in apo AI levels. Similar results were also demonstrated by other studies. PIB surgery is one of the most effective methods for reduction of plasma cholesterol levels, particularly in patients with heterozygous familial hypercholesterolemia. This procedure is also applicable to treatment of sitosterolemia, a rare genetic disorder in which the absorption of plant sterols is abnormally high. Although no major complications of this method have been reported, more extensive studies are required to evaluate its long-term effects on renal and hepatic function. Similarly, long-term impact of this procedure on progression/regression of atherosclerotic lesions must be documented. Finally, indications for this procedure should be carefully considered, particularly in view of availability of other treatments of dyslipidemia.