Mathematical modeling and simulation are well-established and powerful tools to integrate experimental data of individual components of cardiac electrophysiology, excitation-contraction coupling, and regulatory signaling pathways, to gain quantitativeandmechanistic insight into pathophysiological processes and guide therapeutic strategies. Here, we briefly describe the processes governing cardiac myocyte electrophysiology and Ca2+ handling and their regulation, as well as action potential propagation in tissue. We discuss the models and methods used to describe these phenomena, including procedures for model parameterization and validation, in addition to protocols for model interrogation and analysis and techniques that account for phenotypic variability and parameter uncertainty. Our objective is to provide a summary of basic concepts and approaches as a resource for scientists training in this discipline and for all researchers aiming to gain an understanding of cardiac modeling studies.