During vertebrate craniofacial development, neural crest cells (NCCs) contribute much of the cartilage, bone and connective tissue that make up the developing head. Although the initial patterns of NCC segmentation and migration are conserved between species, the variety of vertebrate facial morphologies that exist indicates that a complex interplay occurs between intrinsic genetic NCC programs and extrinsic environmental signals during morphogenesis. Here, we review recent work that has begun to shed light on the molecular mechanisms that govern the spatiotemporal patterning of NCC-derived skeletal structures – advances that are central to understanding craniofacial development and its evolution.