Antiarrhythmic agents exhibit a narrow therapeutic window due to their limited efficacy and high incidence of cardiac and extracardiac side effects. In particular, antiarrhythmic drugs that directly modify cellular electrophysiological properties may cause proarrhythmic effects. Suppression of excitability by Na+ channel block, for instance, will effectively suppress extrasystoles or slow down pacemaker activity but can also enhance reentry arrhythmias by slowing of conduction. Prolongation of action potential duration and effective refractory period by block of K+ channels may cause early after-depolarisations that can initiate torsades de pointes arrhythmia and lead to sudden cardiac death. Proarrhythmic events may afflict all cardiac chambers, however, they are life threatening only when affecting the ventricles. Therefore the concept of “atrial selectivity” has emerged for antiarrhythmic drugs directed against supraventricular tachy-arrhythmias. These drugs target atrial-specific mechanisms of abnormal impulse formation or block ion channels only expressed in the atria in order to avoid ventricular proarrhythmic events. In atrial fibrillation (AF), frequency-dependent Na+ channel blockers exhibit functional atrial selectivity due to their larger effect at high atrial than at slow ventricular excitation rates. The ultraslow outward rectifier K+ current IKur is conducted via Kv1.5 channel that are almost completely absent in human ventricles. This particular channel is targeted by numerous newly developed agents, some of which are truly selective for Kv1.5, however clinical efficacy of these compounds to convert AF into sinus rhythm or preventing recurrence of AF remains to be demonstrated in clinical trials. The acetylcholine-activated inward rectifier K+ channel Kir3.1/3.4 is predominantly expressed in atria, becomes constitutively active during remodelling in persistent AF, and hence may be yet another target for atrial-selective antiarrhythmic drugs. Moreover, several other K+ channels, in particular Ca2+-activated, small conductance K+ (SK) channels are being scrutinized for their contribution to background K+ conductance in human atria and whether they may serve as putative atrial-selective drug targets.