Nitric oxide (NO) synthetized by essentially all cardiac cell types plays a key role in the regulation of cardiac function. Recent evidence shows that NO modulates the activity of cardiac ion channels implicated in the genesis of the cardiac action potential and exerts anti-arrhythmic properties under some circumstances. We review the effects of NO on cardiac ion channels and the signalling pathways, including cGMP-dependent (protein kinase G and cGMP-regulated phosphodiesterases) and cGMP-independent mechanisms (S-nitrosylation and direct effects on G proteins) and finally the role of NO in the genesis of cardiac arrhythmias during ischemia-reperfusion, heart failure, long QT syndrome, atrial fibrillation, and sudden cardiac death.