Thiazolidinediones (TZDs) represent insulin-sensitizing agents that have several pleiotropic properties, possibly related to their favorable effects on cardiovascular remodeling. We briefly describe 2 diabetic patients who experienced a remarkable improvement in their paroxysmal atrial fibrillation (AF) after treatment with rosiglitazone. Current evidence suggests that atrial remodeling represents a prominent mechanism of AF development and perpetuation while inflammation and oxidative stress are possibly implicated in this process. It could therefore be speculated that the pleiotropic effects of TZDs favorably affect atrial remodeling reducing the arrhythmia burden. Further studies are needed in order to elucidate the merit of this pharmacological approach in AF.