The link between plasminogen activator inhibitor (PAI)-1 and the metabolic syndrome with obesity was established many years ago. Increased PAI-1 level can be now considered a true component of the syndrome. The metabolic syndrome is associated with an increased risk of developing cardiovascular disease, and PAI-1 overexpression may participate in this process. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. Interestingly, recent in vitro and in vivo studies showed that besides its role in atherothrombosis, PAI-1 is also implicated in adipose tissue development and in the control of insulin signaling in adipocytes. These findings suggest PAI-1 inhibitors serve in the control of atherothrombosis and insulin resistance.