Caveolins serve as a platform in plasma membrane associated caveolae to orchestrate various signaling molecules to effectively communicate extracellular signals into the interior of cell. All three types of caveolin, Cav-1, Cav-2 and Cav-3 are expressed throughout the cardiovascular system especially by the major cell types involved including endothelial cells, cardiac myocytes, smooth muscle cells and fibroblasts. The functional significance of caveolins in the cardiovascular system is evidenced by the fact that caveolin loss leads to the development of severe cardiac pathology. Caveolin gene mutations are associated with altered expression of caveolin protein and inherited arrhythmias. Altered levels of caveolins and related downstream signaling molecules in cardiomyopathies validate the integral participation of caveolin in normal cardiac physiology. This chapter will provide an overview of the role caveolins play in cardiovascular disease. Furthering our understanding of the role for caveolins in cardiovascular pathophysiology has the potential to lead to the manipulation of caveolins as novel therapeutic targets.