Treatment of cardiovascular diseases relies on the ability not only to abrogate and compensate for congenital deformities but also to repair cardiac pathologies in the adult. Determining how cells communicate within the myocardium and how to use this communication to repair and treat pathological conditions have been necessary steps in the successful intervention of cardiac diseases. In this regard, research has mostly focused on relationships between the main cellular constituents of the heart, myocytes, and fibroblasts. However, the coronary vasculature is also critical to myocardial organization and integrity, and how the vasculature influences and responds to cues from cardiac myocytes and fibroblasts is largely underappreciated. This review discusses how factors that affect myocyte and fibroblast physiology and communication may also interact with the coronary vasculature. Defining the mechanisms of these cellular relationships will help identify ways to control angiogenesis during cardiac remodeling and the development of tissue-engineered therapies.