Since their discovery in the early 1990s, the members of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors have been recognized as therapeutic targets against dyslipidemia and diabetes. Recent studies also identified anti-inflammatory actions of PPARs in cells constituting the atherosclerotic lesion. Delineation of this activity extended the therapeutic potential of PPAR activators beyond their original design as metabolic controllers. The PPAR family consists of 3 PPAR isoforms: α, β/δ, and γ, which exert different and sometimes overlapping effects on whole-body physiology in particular on lipid and glucose metabolism. This review summarizes the current knowledge on the role of PPARs in cardiovascular disease, the metabolic syndrome, atherosclerosis, and cardiac function.