Cardiac mechanical and electrical activities are tightly linked through an intra-cardiac regulatory loop (mechano-electric coupling). This connection is essential for normal heart function and auto-regulation. In diseases associated with altered myocardial mechanical properties or function, however, feedback from the mechanical environment to the origin and spread of excitation can result in deadly cardiac arrhythmias. Ventricular tachyarrhythmias, especially, are encountered in cardiac diseases associated with volume and pressure overload or changes in tissue mechanics. Little is known about the influence of changes in mechano-electric coupling on cardiac rhythm in these settings or the potential therapeutic benefit of its manipulation. Improved understanding may be central to explaining the origin of arrhythmias that occur with these pathologies and to the development of novel mechanics-based therapies. The present review explores the potential role of mechano-electric coupling in ventricular arrhythmogenesis, with a focus on the importance of non-uniformity in mechanical function for the induction and sustenance of ventricular tachyarrhythmias.