The results of the large trials with the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (or statins) in terms of clinical benefits in patients with coronary artery disease indicate that these drugs act in a complex way on several pathways involved in the atherosclerotic process. Beyond their lipid-lowering activity, statins appear to modify many characteristics of the arterial wall, resulting in protection against the progression of plaque growth and/or the precipitation of acute events. The so called "pleiotropic" effects of statins, such as the restoration of endothelial activity, the antioxidant potential or the antiproliferative effect on smooth muscle cells, have been investigated mainly in in vitro experiments. In the near future, it will be necessary to unravel the biological significance and the clinical relevance of these effects, which also involve other pathological conditions such as cancer and osteoporosis. Furthermore, lessons from the trials with statins have allowed a better understanding of the mechanisms leading to atherosclerosis which is now considered as an inflammatory process affecting the vascular wall. This has opened new perspectives in the search for the development of newer and more targeted anti-atherogenic drugs.