The epidemic of metabolic syndrome contributes to the rapid growth of cardiovascular and renal diseases. Hyper-hemodynamics, impaired pressure natriuresis, excess excretory load, insulin resistance, endothelial dysfunction, chronic inflammation, and prothrombotic status individually and interdependently initiate renal injury in metabolic syndrome. The prevention and treatment of kidney disease require a multifactorial approach. Weight loss through diet control and exercise can reverse many pathophysiologic processes. Pharmacologic intervention includes insulin sensitizers, tight glycemic and lipid control, blockage of renin angiotensin aldosterone system, and anti-inflammatory and antithrombotic therapies. Each peroxisome proliferator-activated receptor isoform plays a distinct role in metabolic syndrome, and their agonists may prevent or reverse the early renal injuries.