Thiazolidinediones (TZDs) represent insulin sensitizing drugs that are being increasingly used for the treatment of type 2 diabetes. These agents have also pleiotropic properties that possibly contribute to their favorable cardiovascular effects. In particular, TZDs have anti-inflammatory and anti-oxidant potential while they modulate cardiovascular remodeling. On the other hand, atrial electrical and structural remodeling constitutes the substrate for atrial fibrillation (AF) development and perpetuation. Of note, inflammation and oxidative stress have been recently implicated in the pathogenesis of AF while non-channel blocking drugs with pleiotropic properties, including anti-inflammatory and anti-oxidant, seem to favorably affect atrial remodeling. It is therefore reasonable to assume that TZDs may have a role in the management of AF. Despite some limited observations, no study to date has examined the effect of TZDs therapy on AF development. In addition, the role of these agents in atrial remodeling has not been clarified yet.