Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily that heterodimerize with the retinoid X receptor and bind to specific response elements in target gene promoters. PPARs have three isoforms: alpha, beta (or delta) and gamma. The prostaglandin D(2) metabolite, 15-deoxy-12,14-prostaglandin J(2), is an endogenous ligand for PPARgamma. The antidiabetic thiazolidinediones are synthetic ligands for PPARgamma. PPARgamma is expressed predominantly in adipose tissue and promotes adipocyte differentiation and glucose homeostasis. PPARgamma is also present in various cell types including cardiac myocytes. PPARgamma regulates various neurohumoral factors involved in the progression of heart failure; its ligands inhibit cardiac hypertrophy and ischemia-reperfusion injury via, in part, a PPAR-independent pathway. Although experimental studies suggest that PPARgamma ligands might have a favourable influence on heart failure, their use in patients with heart failure is limited because of an increase in plasma volume. Further studies are needed to determine whether PPARgamma ligands prevent the development of heart disease in clinical settings.