There is a well established association between serum cholesterol and coronary heart disease and this relationship has been found to be related to concentration and is continuous over the entire distribution of cholesterol levels. Recent studies have shown that intensive lipid lowering is beneficial and more stringent guidelines are advocated to improve the clinical outcome. Although statins are the first-line agents for the treatment of hypercholesterolemia, often it is evident that combination therapy is required to achieve the desired reduction in LDL-cholesterol (LDL-C). Niacin and bile acid sequestrants were among the first lipid-lowering drugs developed to lower LDL–C and have been established to be effective in both monotherapy and combination therapy. However, tolerability and compliance issues have limited the use of the traditional bile acid sequestrants. Colesevelam hydrochloride is the newest bile acid sequestrant and shows reduced adverse effects, improved tolerance and better compliance.