The cardiac late sodium current (INa,L) has been in the focus of research in the recent decade. The first reports on the sustained
component of voltage activated sodium current date back to the seventies, but early studies interpreted this tiny current as a product of a
few channels that fail to inactivate, having neither physiologic nor pathologic implications. Recently, the cardiac INa,L has emerged as a
potentially major arrhythmogenic mechanism in various heart diseases, attracting the attention of clinicians and researchers. Research activity
on INa,L has exponentially increased since Ranolazine, an FDA-approved antianginal drug was shown to successfully suppress cardiac
arrhythmias by inhibiting INa,L. This review aims to summarize and discuss a series of papers focusing on the cardiac late sodium
current and its regulation under physiological and pathological conditions. We will discuss critical evidences implicating INa,L as a potential
target for treating myocardial dysfunction and cardiac arrhythmias.