The Purkinje system plays a critical role in spreading activation from the atrioventricular node to the working myocardium throughout the ventricles in normal sinus rhythm. Recent mapping studies have shown that the Purkinje system may be a source of rapid activation in ventricular tachyarrhythmias (VTs) and ventricular fibrillation (VF). Clinical ablation procedures targeting activity in the Purkinje system have successfully treated a subset of VT/VF patients. Animal mapping studies have demonstrated that the Purkinje system may drive the rapid activation rate of VF, particularly after 2-3 minutes of VF. While activation patterns in early VF are consistent with intramural re-entry, in prolonged VF the Purkinje system continues to activate rapidly and drive the activation rate. This edition first published 2013 © 1993, 2009, 2013 Blackwell Publishing Ltd.