Normal cardiac excitation involves an orderly sequence of electrical activation and recovery dependent on the voltage-gated, sodium channels (Na­v1.5). Mutations in Na­v1.5 are associated with arrhythmic conditions such as Brugada Syndrome and progressive cardiac conduction defect which are associated with sudden, often fatal, ventricular tachycardia or fibrillation. The arrhythmic phenotype is associated not only with the primary biophysical change but also additional, anatomical, abnormalities, in turn dependent upon age and sex that themselves exert arrhythmic effects. In this scientific review, we aim to summarize a collection of experimental studies of physiological importance that now provide evidence for a unified binary scheme for the development of arrhythmia. Biophysical studies using mouse Scn5a+/- hearts suggested that Nav1.5 deficiency produces a background electrophysiological defect compromising conduction producing arrhythmic substrate typically unmasked by flecainide or ajmaline challenge. More recent reports further suggest a progressive decline in conduction velocity and increase in its dispersion in Nav1.5 haploinsufficient compared to WT hearts, particularly in ageing male animals. This appears to involve an increased expression of slowly conducting at the expense of rapidly conducting pathways and a demonstrable change in their frequency distributions. These changes were accompanied by increased cardiac fibrosis. It is the combination of the structural and biophysical changes that accentuate arrhythmic substrate to a degree sufficient to cause spontaneous arrhythmic events. This resulting binary scheme explains the requirement for a combination of separate, biophysical and structural, changes, occurring in ageing males associated with Nav1.5 haploinsufficiency, to produce clinical arrhythmia.