Although a persistent component of the sodium current (INaP) was described in cardiac tissue about three decades ago, its physiological role and potential as a therapeutic target was not immediately apparent. Subsequent demonstrations that INaP is enhanced by hypoxia and ischaemia, and that Na+ influx via INaP may contribute to cellular damage, diastolic dysfunction and arrhythmias during ischaemia and reperfusion, raised interest in INaP as a target for anti-ischaemic drugs. Several agents have now been developed to clinical stages, which have INaP block as either their main action, or as a useful co-effect. In this issue of the British Journal of Pharmacology, Vacher et al. report the anti-ischaemic actions of F15845, which appears to exhibit the most selective block of INaP yet described. Its efficacy in animal models of angina raises the prospect of new, specific, INaP blockers that may represent a largely unexploited opportunity for a new class of anti-ischaemic compounds.