The association between increased risk for coronary artery disease (CAD) and elevated plasma cholesterol has been firmly established. The beneficial effect of cholesterol lowering treatment modalities was confirmed in both primary and secondary intervention trials. Because long-term treatment is usually required for lipid lowering therapies the drugs used for lipid reduction have to be not only efficacious but also safe. Inhibitors of cholesterol synthesis that have become clinically available during the last few years, can reduce plasma levels of total cholesterol and low density lipoprotein (LDL)-cholesterol very effectively. In the Familial Atherosclerosis Treatment Study (FATS) an intensive cholesterol lowering treatment modality consisting of a combination of an inhibitor of cholesterol synthesis and colestipol reduced the progression of coronary lesions and caused a partial regression of such lesions. Among the various inhibitors of cholesterol synthesis developed recently, pravastatin appears to be tissue-specific because of its hydrophilic property.