Computational cardiology is the scientific field devoted to the development of methodologies that enhance our mechanistic understanding, diagnosis and treatment of cardiovascular disease. In this regard, the field embraces the extraordinary pace of discovery in imaging, computational modeling and cardiovascular informatics at the intersection of atherogenesis and vascular biology. This article highlights existing methods, practices, and computational models and proposes new strategies to support a multidisciplinary effort in this space. It focuses on the means by which to leverage and coalesce these multiple disciplines to advance translational science and computational cardiology. Analyzing the scientific trends and understanding the current needs, it presents the authors’ perspective for the future of cardiovascular treatment.