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The hierarchical construction of the myocardium plays a pivotal role in the biomechanics of the heart muscle and the resulting flow of blood. In disease, the construction of the heart remodels, altering the structure of the tissue from the subcellular level all the way to the whole organ. Elucidating the impact of these fundamental alterations on the biomechanics of the heart presents challenges to diagnosis, therapy planning, and treatment. Computational modeling provides an innovative tool, enabling the simulation of complex biomechanics that capture the complexity of tissue, its growth and remodeling, and the resulting blood flow. In this chapter, we review the key ways that computational models can address challenging biomechanical questions in the heart and how these tools can change the way treatment is approached across a range of heart diseases.