Phytosterols, which are structurally related to cholesterol, are found in all plant foods with highest concentration occurring in vegetable oils and nuts. Phytosterols are known to reduce serum low-density lipoprotein cholesterol level without changing high-density lipoprotein cholesterol or triglyceride levels. Daily consumption of phytosterols-enriched foods is widely used as a therapeutic option to lower plasma cholesterol and atherosclerotic disease risk. The cholesterol-lowering action of phytosterols is thought to occur, at least in part, through competitive replacement of dietary and biliary cholesterol in mixed micelles, which undermines the absorption of cholesterol. The aim of this review is to provide a general overview of available evidence regarding the effects of phytosterols on cholesterol metabolism and addressing issues related to efficacy as dose, length, frequency of consumption, type of phytosterol (sterols versus stanols) or food matrix. Furthermore, we will explore the factors that influence the response of individuals to phytosterol therapy and evaluate their safety and the possibility that elevated plasma phytosterol concentrations contribute to the development of premature coronary artery disease.