It is well known that cardiac neural crest participates in development of the cardiac outflow septation and patterning of the great arteries. Less well known is that ablation of the cardiac neural crest leads to a primary myocardial dysfunction. Recent data suggests that the myocardial dysfunction occurs because of the absence of an interaction of neural crest and pharyngeal endoderm to alter signaling from the endoderm. Continuation of an FGF-like signal from the endoderm past a precise time in development appears to be detrimental to myocardial maturation.