Postnatally, heart muscle cells almost completely lose their ability to divide, which makes their loss after trauma irreversible. Potential repair by cell grafting or mobilizing endogenous cells is of particular interest for possible treatments for heart disease, where the poor capacity for cardiomyocyte proliferation probably contributes to the irreversibility of heart failure. Knowledge of the molecular mechanisms that underly formation of heart muscle cells might provide opportunities to repair the diseased heart by induction of (trans) differentiation of endogenous or exogenous cells into heart muscle cells. We briefly review the molecular mechanisms involved in early development of the linear heart tube by differentiation of mesodermal cells into heart muscle cells. Because the initial heart tube does not comprise all the cardiac compartments present in the adult heart, heart muscle cells are added to the distal borders of the tube and within the tube. At both distal borders, mesodermal cell are recruited into the cardiac lineage and, within the heart tube, muscular septa are formed. In this review, the relative late additions of heart muscle cells to the linear heart tube are described and the potential underlying molecular mechanisms are discussed.