Since their first description five years ago, knowledge about human atrial 5-HT4 receptors has increased considerably. Progress has been facilitated by the advent of selective antagonists with high affinity for human atrial 5-HT4 receptors. The receptors have been detected in both right and left atrium where they mediate increases in contractile force. Human sinoatrial 5-HT4 receptors may mediate the tachycardia caused by 5-HT and cisapride, and 5-HT elicits arrhythmias via 5-HT4 receptors in human atrium. In this article, Alberto Kaumann suggests that 5-HT may be involved in the genesis of atrial fibrillation and associated thromboembolic stroke and that both the arrhythmia and stroke could be prevented by inhibiting 5-HT4 receptors.