Adiponectin is a protein secreted by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders characterized by insulin resistance including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with both decreased adiponectin levels and endothelial dysfunction. Recent studies demonstrate that adiponectin has insulin-sensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, diabetes, and coronary heart disease have important effects in increasing adiponectin levels, decreasing insulin resistance, and improving endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for understanding and treating atherosclerosis and coronary heart disease.