Morphogenesis of the cardiac outflow tract and aortic sac regions requires the progressive immigration and integrated differentiation of cells having very divergent embryonic histories. Mesodermal cells originating both within and beside the developing head contribute to endocardium and myocardium. These cells, together with later arriving neural crest cells, participate in the formation of the aorticopulmonary septum, truncal cushions, and semilunar valves, although there is uncertainty regarding the precise contributions of each. In addition, precursors of the enveloping epicardium and coronary arteries move into the outflow tract. Defining the spatial and temporal contributions of these disparate populations and the boundaries between them as the outflow tract shifts caudally is an essential prerequisite to understanding normal heart morphogenesis as well as the etiology of outflow tract dysmorphologies.