Phytosterols or plant sterols have long been known to lower serum cholesterol concentrations by competing with dietary and biliary cholesterol for intestinal absorption. Food products containing phytosterols and phytostanols are now available to assist in lowering blood cholesterol levels. In contrast to these possibly beneficial effects of plant sterols, a rare genetic condition called sitosterolemia, an autosomal recessive disorder also known as phytosterolemia, is characterized by over absorption of phytosterols and premature coronary artery and aortic valve disease. Phytosterols have also recently been identified in atheromatous plaque obtained from individuals with apparently normal absorption of plant sterols raising the possibility that phytosterols are a novel atherosclerotic risk factor. This article reviews phytosterols and their relationship to vascular disease.