Excitation–contraction coupling is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca²⁺ across the sarcolemma triggering Ca²⁺ release from the sarcoplasmic reticulum (SR) – a process termed Ca²⁺‐induced Ca²⁺ release (CICR) – followed by re‐sequestration of Ca²⁺ into the SR. The Na⁺/Ca²⁺ exchanger inextricably couples the cycling of Ca²⁺ and Na⁺ in cardiac myocytes. Thus, influx of Na⁺ via voltage‐gated Na⁺ channels (Na_V) has emerged as an important regulator of CICR both in health and in disease. Recent insights into the subcellular distribution of cardiac and neuronal Na_V isoforms and their ultrastructural milieu have important implications for the roles of these channels in mediating Ca²⁺‐driven arrhythmias. This review will discuss functional insights into the role of neuronal Na_V isoforms vis‐à‐vis cardiac Na_Vs in triggering such arrhythmias and their potential as therapeutic targets in the context of the aforementioned structural observations.