This review introduces the disease state of diabetes mellitus and provides a background of the impact of the disease on the population, its biology and pathophysiology, and the current treatment strategies for treating diabetes. In Europe, the thiazolidine dione derivatives pioglitazone and rosiglitazone have been approved for the treatment of type 2 diabetes mellitus either as monotherapy for patients with intolerance or contraindications to metformin or in combination therapy. Modifications of thiazolidinediones have proven highly effective and do not exhaust the possible changes that can be made to improve potency, safety and efficacy of these thiazolidinedione derivatives. TZDs have been approved for type 2 diabetes mellitus, particularly for overweight patients who are inadequately controlled by diet and exercise alone, for which metformin and sulphonylurea are inappropriate because of contraindications or intolerance. This class of drugs seems particularly suited for obese patients, but is currently not considered as a first choice for monotherapy. The efficacy with respect to blood glucose lowering is comparable with sulphonylurea (SU) derivatives and with metformin. Long-term data with respect to efficacy and side effects are still limited. This is the updated report on thiazolidinediones and explained its efficacy and how it is better than other antidiabetic agents.