Atherosclerosis of the large arteries is the main origin of cerebro- and cardiovascular diseases, the leading causes of mortality and morbidity in industrialized countries. The pathophysiology of coronary and cerebrovascular atherosclerosis is multifactorial and complex. Fibrates are hypolipidemic drugs that lower progression of atherosclerotic lesions mainly through activation of the nuclear receptor peroxisome-proliferator activated receptor-alpha. In addition, fibrates exert pleiotropic and anti-inflammatory actions. In this chapter, we will focus on the different effects of fibrates impacting on the development of atherosclerosis.