Although plant sterols (phytosterols) and cholesterol have similar chemical structures, they differ markedly in their synthesis, intestinal absorption, and metabolic fate. Phytosterols inhibit intestinal cholesterol absorption, thereby lowering plasma total and low-density lipoprotein (LDL) cholesterol levels. In 16 recently published human studies that used phytosterols to reduce plasma cholesterol levels in a total of 590 subjects, phytosterol therapy was accompanied by an average 10% reduction in total cholesterol and 13% reduction in LDL cholesterol levels. Phytosterols may also affect other aspects of cholesterol metabolism that contribute to their antiatherogenic properties, and may interfere with steroid hormone synthesis. The clinical and biochemical features of hereditary sitosterolemia, as well as its treatment, are reviewed, and the effects of cholestyramine treatment in 12 sitosterolemic subjects are summarized. Finally, new ideas for future research into the role of phytosterols in health and disease are discussed.