Inspired by studies demonstrating the potential for new myocyte formation within adult mammalian hearts, an ongoing explosion of research is elucidating the biology of cardiac myogenesis and angiogenesis. Multiple lines of research suggest that disease-associated activation of endogenous cardiac repair processes are often insufficient to overcome the cell death resulting from myocardial infarction and chronic heart failure. In this context, this review highlights current evidence supporting endogenous cardiac repair mechanisms in human hearts, recent progress with clinical application of myocardial cell therapy, and complementary efforts to manipulate endogenous myocardial repair processes using a variety of tissue engineering strategies. The goal of this overview is to demonstrate that the insights and opportunities derived from each of these lines of inquiry are mutually complementary for ultimately achieving the goal of therapeutic cardiac regeneration.