Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand activated transcription factor known to regulate fatty acid metabolism. Thiazolidinediones (TZDs), PPARγ synthetic agonists, currently used to treat patients with type 2 diabetes, have been shown to lower the blood pressure and protect against vascular diseases such as atherosclerosis. In line with these findings, it has been reported that individuals with loss-of-function mutations of PPARγ developed sever early-onset hypertension in addition to metabolic abnormalities. Accumulating evidences suggest PPARγ in the vasculature has protective effects on cardiovascular disease despite unclear mechanism. Because of ubiquitous expression of PPARγ, TZDs are well-known to be associated with serious side effects such as weight gain, fluid retention, and bone fractures. Thus identification of mechanisms on tissue-specific PPARγ activity may lead to the development of targeted treatment which is characterized by no deleterious effects. This review discusses role of PPARγ in cardiovascular disease.