In 2000, two new thiazolidinediones, pioglitazone and rosiglitazone, were approved for the treatment of type 2 diabetes mellitus (T2DM). Administered as monotherapy or in combination with other antihyperglycemic agents, they represented an effective option for achieving or maintaining good glycemic control in patients with T2DM. Despite their efficacy, there was increasing concern regarding the potential of an increased cardiovascular risk with rosiglitazone. This resulted in the suspension of rosiglitazone from the European market by the European Medicines Agency in September 2010. This article focuses on the various steps that led to this important decision, and discusses a possible alternative for the treatment of patients receiving rosiglitazone.