It is noteworthy that drugs having a significant impact in preventing arrhythmias (atrial or ventricular) are those with no direct specific antiarrhythmic electrophysiologic properties. Specifically, drugs able to interfere with the renin-angiotensin system and the n-3 fatty acids seem to play a relevant role as antiarrhythmics, even if they do not act in the typical manner. Angiotensin-converting enzyme (ACE) inhibitors decrease the incidence of arrhythmias in patients with decreased left ventricular function. The main reduction is linked to a decrease of ventricular arrhythmias, while several studies have suggested that ACE-inhibitors may also decrease the burden of atrial fibrillation. Furthermore, many of angiotensin receptor blockers and spironolactone have been shown to have antiarrhythmic properties. n-3 polyunsaturated fatty acids (PUFAs) are known to be antiarrhythmic as well. Their effects on the fast voltage-dependent sodium current I(NA), inhibition of I(Ca2+) and the K+ channel modulation explain their antiarrhythmic properties. For these reasons the renin-angiotensin system blockade and the n-3 PUFA intake may provide simple and safe protection from cardiac arrhythmias.