A critical contribution of neural crest to the developing cardiovascular system has been recognized for nearly 25 years. Recently, however, advanced mouse genetic techniques have revealed a series of previously unrecognized molecular pathways that regulate cardiac neural crest migration and differentiation. These involve members of the bone morphogenetic protein (BMP), T‐box, myocardin, Gata and Notch families. In addition, molecules previously studied for their role in axon guidance have now been implicated in neural crest and cardiovascular patterning. In particular, members of the semaphorin family of secreted guidance molecules, along with plexin and neuropilin receptors, play critical roles during aortic arch remodelling and are implicated as candidate genes for contribution to congenital heart disease.