The thiazolidinedione rosiglitazone maleate works primarily to improve insulin sensitivity in muscle and adipose tissue. It may have additional pharmacologic effects, however, as its main target is peroxisome proliferator-activated receptor-gamma. Data using the homeostasis model assessment and proinsulin:insulin ratio in patients with type 2 diabetes mellitus suggest that rosiglitazone may have the potential to sustain or improve beta-cell function. In these patients the drug reduces fasting plasma glucose, glycosylated hemoglobin, insulin, and C-peptide. In clinical trials, rosiglitazone monotherapy significantly reduced glycosylated hemoglobin by 1.5% compared with placebo and led to significant improvements in glycemic control when given in combination with metformin, sulfonylureas, or insulin. A dosage of 4 mg twice/day significantly reduced fasting plasma glucose levels and produced comparable reductions in glycosylated hemoglobin compared with glyburide. Rosiglitazone has a low risk of gastrointestinal side effects and hypoglycemia, reduced insulin demand, potential sparing effects on beta-cells, and favorable drug interaction profile. Adverse events of clinical significance are edema, anemia, and weight gain. Premarketing data indicate no significant difference in liver enzyme elevations for rosiglitazone, placebo, or active controls. Another drug in the thiazolidinedione class, troglitazone, was associated with idiosyncratic hepatotoxicity and was removed from the market. Therefore, until long-term data are available for rosiglitazone, liver enzyme monitoring is recommended.