Diabetes mellitus is a chronic, progressive disease that results in microvascular and macrovascular complications. Patients with diabetes are at high risk for developing heart failure, and the prevalence of diabetes in patients with heart failure ranges from 24% to 44%, with an estimated 1 to 2 million individuals in the United States having both diabetes and heart failure. Patients with diabetes and heart failure are at increased risk for mortality. Primary treatment goals in diabetes include restoration and maintenance of normoglycemia, avoidance of diabetic complications, and prevention of cardiovascular events. The range of therapeutic options for glycemic control has been extended with the introduction of thiazolidinediones (TZDs) used as monotherapy or in combination with other oral antidiabetic medications or insulin. TZDs decrease plasma insulin levels, improve endothelial function, decrease vascular inflammation, and decrease C-reactive protein levels, effects that are potentially beneficial in patients with heart failure. Weight gain and peripheral edema are recognized side effects of these drugs, particularly when used in combination with insulin. Although health care providers should be aware of the potential risk of worsened heart failure when TZDs are used in patients with diabetes and heart failure, these agents may be considered for use in patients with New York Heart Association class I and II heart failure when appropriate monitoring can be provided. Prospective clinical trials are currently under way to further define the cardiovascular safety and efficacy of TZDs in diabetic patients with heart failure.