Cholesterol is a 27-carbon steroid that is an essential component of the cell membrane, the immediate precursor of steroid hormones, the substrate for the formation of bile acids, and is required for the assembly of very low density lipoprotein in the liver. Because as much as two-thirds of total body cholesterol in patients is of endogenous origin, an effective means to control cholesterogenesis may occur by inhibition of its biosynthesis. Cholesterol is biosynthesized in a series of more than 25 separate enzymatic reactions that initially involve the formation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA). Early attempts to pharmacologically block cholesterol synthesis focused only on steps later in the biosynthetic pathway and resulted in compounds with unacceptable toxicity. Recent research had identified that HMG CoA reductase is a key rate-limiting enzyme in this pathway and is responsible for the conversion of HMG CoA to mevalonate. Additional research with fungal metabolites identified a series of compounds with potent inhibiting properties for this target enzyme, from which lovastatin was selected for clinical development. A reduction in cholesterol synthesis by lovastatin has been subsequently confirmed in cell culture, animal studies and in humans. A resultant decrease in circulating total and low-density lipoprotein (LDL) cholesterol has also been demonstrated in animals and humans. Because hepatic LDL receptors are the major mechanism of LDL clearance from the circulation, further animal research has confirmed that these declines in cholesterol are accompanied by an increase in hepatic LDL receptor activity. Lovastatin effectively diminishes endogenous cholesterol synthesis providing useful therapeutic properties for patients with hypercholesterolemia.