The cardiac conduction system (CCS) includes the sinus node, atrioventricular (AV) node and His-Purkinje system (Boyett, 2009). The CCS is associated with a wide range of arrhythmias: dysfunction of the sinus node results in sinus bradyarrhythmias and tachyarrhythmias; the AV node is the substrate of AV nodal reentrant tachycardia (AVNRT) and dysfunction of the AV node results in heart block; the His-Purkinje system is prone to afterdepolarizations and torsades de pointes and it can be the substrate of reentrant arrhythmias and dysfunction of the system results in bundle branch block. However, the CCS also includes lesser-known tissues, including paranodal tissue running alongside the sinus node, AV ring tissues running around the AV valves and nodal-like tissue in the ventricular outflow tract. Like the main components of the CCS, the additional components arise from ‘primary myocardium’ (as distinct from ‘working myocardium’) in the embryo. These extra tissues are also likely to be involved in arrhythmogenesis. The paranodal tissue is potentially responsible for the ‘cristal tachycardias’ (a class of atrial tachycardias) and the AV ring tissues are known to be responsible for other atrial tachycardias (the right AV ring especially constitutes ‘a ring of fire’). We hypothesise that the nodal-like tissues in the ventricular outflow tract are responsible for the highly arrhythmogenic nature of the right ventricular outflow tract in general and the ventricular outflow tract ventricular tachycardias in particular. In general, the arrhythmogenic nature of the CCS is largely the consequence of the unique electrophysiological phenotype of the CCS and its well known propensity for pacemaking. This in turn is a consequence of the unique pattern of expression of ion channels, Ca2+-handling proteins and gap junction channels in the CCS. We have shown that the expression profiles of the sinus node, AV node, Purkinje fibres, paranodal tissue, AV ring tissues and nodal-like tissue in the ventricular outflow tract have features in common and which are distinct from those of the working myocardium (e.g. Chandler et al., 2009). For example, many of them express the pacemaker ion channel, HCN4, and all show poor expression of the inward rectifier K+ channel, Kir2.1, and all the nodal and nodal-like tissues lack expression of the Na+ channel, Nav1.5, and the gap junction channel, Cx43. In part, it is the expression of HCN4 and/or poor expression of Kir2.1 that is responsible for the propensity for pacemaking. It is the lack of expression of Nav1.5 and Cx43 at the AV node that is in part responsible for AVNRT. However, AVNRT is also the result of the highly complex three-dimensional structure of the CCS at the AV junction – at this point, there is an intersection of the AV ring tissues, AV node and bundle of His. We are generating detailed three-dimensional anatomical models of all parts of the CCS (e.g. Li et al., 2008). Computer simulation has confirmed that it is possible to explain AVNRT based on the combination of the complex structure of the CCS at the AV junction together with the equally complex pattern of expression of ion channels and gap junction channels at the AV junction (Li et al., 2008; Inada et al., 2009). Dysfunction of the CCS can be hereditary, but it is primarily a disease of ageing – the incidence of sinus bradycardia, heart block and bundle branch block all increase with ageing. This is why electronic pacemakers are primarily fitted to the elderly. In addition, we and others have associated dysfunction of the CCS with heart failure, myocardial infarction, pulmonary hypertension, atrial fibrillation, diabetes, possibly obesity and, surprisingly, athletic training. For example, former professional cyclists show a higher incidence of sick sinus syndrome and pacemaker implantation (Baldesberger et al., 2008). Previously, the dysfunction of the CCS has been explained by ‘fibrosis’ and, as an example, there is well documented fibrosis in the sinus node of the ageing mouse (Hao et al., 2011). However, in many instances, there is no evidence of fibrosis, for example in the sinus node of the ageing human (Alings et al., 1995). Furthermore, even in cases in which fibrosis is documented, the importance of the fibrosis is questionable. This is because in all investigated instances (ageing, heart failure, myocardial infarction, pulmonary hypertension, atrial fibrillation and athletic training) there is a widespread remodelling of ion channels, Ca2+-handling proteins and gap junction channels. For example, in many instances, there is a downregulation of HCN4. Computer simulation has shown that the remodelling can explain the dysfunction of the CCS (e.g. Hao et al., 2011). In summary, mapping of ion channels, Ca2+-handling proteins and gap junction channels throughout the CCS in health and disease (as well as mapping of anatomy), often in combination with computer simulation, is shedding new light on CCS-related arrhythmias.