Ranolazine which is currently approved as an antianginal agent reduces the Na-dependent Ca overload via inhibition of the late sodium current (late I_Na) and thus improves diastolic tone and oxygen handling during myocardial ischemia. According to accumulating evidence ranolazine also exerts beneficial effects on diastolic and systolic heart failure where late I_Na was also found to be elevated. Moreover, late I_Na plays a crucial role as an arrhythmic substrate. Ranolazine has been described to have antiarrhythmic effects on ventricular as well as atrial arrhythmias without any proarrythmia or severe organ toxicity as it is common for several antiarrhythmic drugs. In patients with diabetes, treatment with ranolazine led to a significant improvement of glycemic control. In this article possible new clinical indications of the late I_Na-inhibitor ranolazine are reviewed. We summarize novel experimental and clinical studies and discuss the significance of the available data.