Nearly 1 in 4 adults in the United States is obese. The connection between obesity and insulin resistance, type 2 diabetes, and cardiovascular disease is a well researched one. The increasing prevalence of each of these diseases has become a growing concern for the medical community. Adiponectin is a collagen-like plasma protein secreted by adipocytes that has been suggested to play a causal role in the development of insulin resistance and cardiovascular disease. The protein has been found to be decreased in cases of insulin resistance, diabetes, atherosclerosis, and coronary artery disease. Up-regulation of adiponectin and its receptor, through the use of thiazolidinediones, has been found to be partially related to insulin sensitization and thus antidiabetic effects. In this review, we discuss adiponectin’s antiatherogenic effects, its association with insulin resistance and obesity, and the possibility of using adiponectin and its receptor as a therapeutic target.