Calcium is critical to a wide range of physiological processes, including neurological function, immune responses, and muscle contraction in the heart. Calcium-dependent signaling pathways driving these functions enlist a variety of proteins and channels that must rapidly and selectively bind calcium against thousand-fold higher cation concentrations. Frequently these pathways further rely on co-localization of these proteins within specialized subcellular structures to function properly. Our lab has developed multi-scale simulation tools to understand calcium homeostasis and its dysregulation at the molecular through systems levels. Applications include molecular simulations to predict protein-protein interactions, reaction-diffusion simulations that leverage high-resolution microscopy data and computer vision techniques to characterize morphological differences in cells important to their function. In this seminar, I will describe these tools and their applications to a calcium-dependent signaling pathway driven by calmodulin and calcineurin activation, which is important in cardiac development and hypertrophy.