Carotenoids are a class of natural, fat-soluble pigments found principally in plants. They have potential antioxidant biological properties because of their chemical structure and interaction with biological membranes. Epidemiologic studies supported the hypothesis that antioxidants could be used as an inexpensive means of both primary and secondary cardiovascular disease (CVD) prevention. In fact, the oxidation of low-density lipoproteins (LDL) in the vessels plays a key role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by high dietary antioxidant intake, so that carotenoids, as part of food patterns such as the Mediterranean diet, may have beneficial effects on cardiovascular health too. Further properties of carotenoids leading to a potential reduction of cardiovascular risk are represented by lowering of blood pressure, reduction of pro-inflammatory cytokines and markers of inflammation (such as C-reactive protein), and improvement of insulin sensitivity in muscle, liver, and adipose tissues. In addition, recent nutrigenomics studies have focused on the exceptional ability of carotenoids in modulating the expression of specific genes involved in cell metabolism. The aim of this review is to focus attention to this effect of some carotenoids to prevent CVD.