Patients with the metabolic syndrome are insulin resistant and manifest a cluster of risk factors for cardiovascular disease. Impaired fibrinolysis and increased concentrations in blood of plasminogen activator inhibitor-1 (PAI-1) are related to insulin resistance and abdominal obesity and may contribute to the increased risk for cardiovascular disease in this group. Weight loss, metformin, and thiazolidinediones ameliorate insulin resistance and decrease concentrations of PAI-1. Thus, they may lower risk in patients with the metabolic syndrome.