The benefits of the cholesterol lowering effects of the 3-hydroxy-3-methylglutaryl coenzymeA reductase inhibitors class of drugs (statins) in reducing morbidity and mortality related to cardiovascular disease have been well documented in large scale clinical trials and these drugs are therefore widely prescribed in patients with elevated cholesterol levels to lower their risk of vascular disease. However, several trials have suggested that the benefits derived from the statins may not be related to their cholesterol lowering effects alone. Statins may also have important anti-inflammatory properties and effects related to their interruption of the process of prenylation of the small signaling proteins, Ras and Rho. This review focuses on these cholesterol-independent effects and their relationship to vascular disease, in particular investigating the evidence for such effects at a cellular level, the published trials that study the pleiotropic effects of statin therapy on vascular disease and the possibilities of extending current knowledge into novel, more focused therapies.