Mammalian physiological processes, and likely any organism with a biliary tree, can distinguish between dietary cholesterol and non-cholesterols, retaining very little of the non-cholesterol in their bodies. Historically, the distinction between plant sterols and cholesterol has been known about for a century or more. That plants sterols were not 'absorbed' has been investigated for almost half a century. Indeed, the oral of plant sterols in gram quantities was shown to interfere with cholesterol absorption and is one of the oldest pharmacological therapies for hypercholesterolemia. Although the basis for the latter was shown to be caused by exclusion of cholesterol from intestinal micelles by plant sterols, it was not until the identification of the a rare genetic disease, sitosterolemia, first described in 1974, that led to the hypothesis that specific molecular mechanism(s) governed both the entry and excretion of sterols by the body. This talk will cover the physiology of dietary sterol metabolism, genetics and pathophysiology of sitosterolemia. Additionally, the role of plant sterols in normal and abnormal metabolism in humans as well as selected animal models will be discussed.