Elevated levels of plasma LDL cholesterol (LDL-C) represent a major risk factor for cardiovascular disease. Treatments aimed at reducing levels of circulating LDL are regarded, therefore, as cardioprotective. The cholesterol lowering properties of plant sterols have been known for some time and many clinical studies have confirmed the efficacy of sitosterol in lowering plasma LDL-C concentrations. Animal studies have also shown reductions in LDL by sitosterol. The use of animal models has been useful in facilitating the elucidation of specific mechanisms by which this sterol exerts its hypocholesterolemic action. It is well known that plant sterols compete with cholesterol for space within bile salt micelles in the intestinal lumen thereby reducing cholesterol absorption. The understanding of the function of plant sterols in impeding cholesterol absorption has been clarified with the discovery of the adenosine binding cassette transporters, ABCG5/8, involved in the regulation of sterol absorption and secretion into the enterocyte and hepatocyte. Compared to cholesterol and other sterols, sitosterol is preferentially pumped out to the intestinal lumen by the ABCG5/8 transporters. This selective binding of sitosterol to the transporters ultimately results in significant lowering of plasma cholesterol. However, some findings support the hypothesis that plant sterols might be an additional risk factor for coronary heart disease. From the review of these studies, it is apparent that sitosterol is a useful dietary supplement for the lowering of plasma cholesterol. Nevertheless, this plant sterol should be used with caution in certain individuals who have a higher absorption rate of sitosterol.