The heart is a complex organ system composed of a highly diverse set of muscle and nonmuscle cells. Understanding the pathways that drive the formation, migration, and assembly of these cells into the heart muscle tissue, the pacemaker and conduction system, and the coronary vasculature is a central problem in developmental biology. Efforts to unravel the biological complexity of in vivo cardiogenesis have identified a family of closely related multipotent cardiac progenitor cells. These progenitors must respond to non-cell-autonomous signaling cues to expand, differentiate, and ultimately integrate into the three-dimensional heart structures. Coupling tissue-engineering technologies with patient-specific cardiac progenitor biology holds great promise for the development of human cell models of human disease and may lay the foundation for novel approaches in regenerative cardiovascular medicine.