Atrial fibrillation (AF) is the most common sustained clinical tachyarrhythmia. AF is a progressive condition as demonstrated by the finding that maintenance of normal rhythm and contractile function becomes more difficult the longer AF exists. AF causes cellular stress, which induces atrial remodelling, involving reduction in the expression of L-type Ca(2+) channels and structural changes (myolysis), finally resulting in contractile dysfunction. Heat shock proteins (HSPs) comprise a family of proteins involved in the protection against different forms of cellular stress. Their classical function is the prevention of toxic protein aggregation by binding to (partially) unfolded proteins. Recent investigations reveal that HSPs prevent atrial remodelling and attenuate the promotion of AF in both cellular and animal experimental models. Furthermore, studies in humans suggest a protective role for HSPs against progression from paroxysmal AF to chronic, persistent AF. Therefore, manipulation of the HSP system may offer novel therapeutic approaches for the prevention of atrial remodelling. Such approaches may contribute to the maintenance or restoration of tissue integrity and contractile function. Ultimately, this concept may offer an additional treatment strategy to delay progression towards chronic AF and/or improve the outcome of cardioversion.