Cardiac neural crest cells (NCCs) are a transient, migratory cell population exclusive to vertebrate embryos. Ablation, transplantation, and lineage-tracing experiments in chick and mouse have demonstrated their essential role in the remodeling of the initially bilateral and symmetric pharyngeal artery pairs into an aortic arch and for the septation of the cardiac outflow tract into the base of the pulmonary artery and aorta. Accordingly, defective cardiac NCC function is a common cause of congenital birth defects. Here, we review our current understanding of cardiac NCC-mediated vascular remodeling and signaling pathways important for this process. We additionally discuss their contribution to the cardiac valves as well as the still contentious role of cardiac NCCs in the development of the myocardium and conductive system of the heart.