To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people. Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress. Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.