Low levels of adiponectin, a fat-derived hormone, are found in coronary heart disease, type 2 diabetes, obesity, and other insulin-resistant states. Conversely, high adiponectin levels are predictive of reduced coronary risk in long-term epidemiologic studies. A close association between hypoadiponectinemia and endothelial dysfunction has also been demonstrated. The various mechanisms through which adiponectin may protect the endothelium, via its insulin-sensitizing, antiatherogenic, anti-inflammatory, and antioxidant properties, are reviewed.