Abstract Atherosclerotic cardiovascular disease in the elderly is the result of several decades of cholesterol accretion. Advanced lesions may not be amenable to treatment, but a reversal of cholesterol accumulation may be possible. High-density lipoproteins (HDL) could serve an important function in this reversal through their role in the process of reverse cholesterol transport, which removes cholesterol from the body. Reverse cholesterol transport could be stimulated by raising plasma HDL level, but the efficacy of the process may be determined by the way in which HDL level is elevated. The increase of HDL synthesis rate may be the best approach. The antiatherosclerotic effects of gemfibrozil, a lipid-lowering agent that appears to raise HDL synthesis rate, may be mediated through this mechanism.