The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in cardiovascular disease have generally been attributed to their cholesterol-lowering property. However, an increasing number of in vitro and in vivo studies indicate that statins have direct anti-inflammatory effects that are not mediated by their hypocholesterolemic activity. In this article, the HMG-CoA-reductase-dependent and -independent mechanisms by which statins might affect leukocyte adhesion and migration to sites of inflammation are reviewed and the implications for the design of new statin-derived drugs are discussed.