The Na current (INa) in human ventricle is carried through a specific isoform of the voltage gated Na channel in heart. The pore forming α-subunit is encoded by the gene SCN5A. Up to four β-subunits may be associated, and the larger macromolecular complex may include attachments to cytoskeleton and scaffolding proteins, all of which may affect the gating kinetics of the current. INa underlies initiation and propagation of action potentials in the heart and plays a prominent role in cardiac electrophysiology and arrhythmia. In addition, INa also loads the ventricular cell with Na+ ions and plays an important role in intracellular Na homeostasis. This review considers the structure and function of the human cardiac Na channel that carries INa with a particular consideration of the implications of alterations in INa in acquired cardiac diseases such as hypertrophy, failure, and ischemia, which affect Na loading.