Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low‐density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health‐promoting effects of PSs include anti‐obesity, anti‐diabetic, anti‐microbial, anti‐inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol‐rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.