Even after over a century of active research, the heart continues to reveal new complexities in behavior and remains difficult to understand fully. Multi-scale dynamics ranging from cellular and subcellular behavior to chambers of the heart and the full organ make analysis complicated. In addition, different types of heart functions, including electrical wave signaling, mechanical contraction, and blood flow, present separate challenges. Theory, numerical modeling, and experiments provide different contributions to our understanding of cardiac processes and behavior. This Focus Issue includes papers from across all these spectra and addresses a number of interesting open questions regarding the complex dynamics of the heart.