Ranolazine is currently approved for use in chronic angina. The basis for this use is likely related to inhibition of late sodium channels with resultant beneficial downstream effects. Randomized clinical trials have demonstrated an improvement in exercise capacity and reduction in angina episodes with ranolazine. This therapeutic benefit occurs without the hemodynamic effects seen with the conventional antianginal agents. The inhibition of late sodium channels as well as other ion currents has a central role in the potential use of ranolazine in ischemic heart disease, arrhythmias, and heart failure. Despite its QTc-prolonging action, albeit minimal, clinical data have not shown a predisposition to torsades de pointes, and the medication has shown a reasonable safety profile even in those with structural heart disease. In this article we present the experimental and clinical data that support its current therapeutic role, and provide insight into potential future clinical applications.