Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation–contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation–contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.