Our understanding of the metabolic syndrome has been improved by the discovery nuclear peroxisome proliferator-activated receptors (PPARs). PPAR-γ is a nuclear receptor that influences the expression of multiples gene involved in carbohydrate and lipid metabolism. At the crossroads of obesity, insulin resistance, and cardiovascular disease is the nuclear receptor PPAR-γ. At present, metabolic syndrome can be described as a 'PPAR-γ agonist resistance syndrome.' The modulation of PPAR-gamma activity is an interesting therapeutic approach to address multi-component metabolic syndrome and its consequent cardiovascular events.