The molecular basis of the processes of cholesterol absorption and plasma plant sterol levels is only partially understood. A breakthrough in understanding the molecular basis of sterol absorption has recently achieved by the discovery of ABCG5 and ABCG8. The genes involved in cholesterol absorption and plant sterols metabolism are characterized by a spectrum of specificity. Studies on a recently developed novel cholesterol absorption-blocking agent, ezetimibe, provide additional insight into the genetics of cholesterol absorption and plasma plant sterol levels. Focuses on the evidence for genetic control of cholesterol absorption and plasma plant sterol levels are reviewed. The commonalities and difference in the regulation of these two traits are examined and the recent developments and future perspectives in this field are discussed.