Common causes of heart failure are associated with derangements in myocardial fuel utilization. Evidence is emerging that metabolic abnormalities may contribute to the development and progression of myocardial disease. The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors has been shown to regulate cardiac fuel metabolism at the gene expression level. The three PPAR family members (alpha, beta/delta and gamma) are uniquely suited to serve as transducers of developmental, physiological, and dietary cues that influence cardiac fatty acid and glucose metabolism. This review describes murine PPAR loss- and gain-of-function models that have shed light on the roles of these receptors in regulating myocardial metabolic pathways and have defined key links to disease states including the hypertensive and diabetic heart.