Craniofacial mesenchyme is heterogeneous with respect to origins (e.g., paraxial mesoderm, lateral mesoderm, prechordal mesoderm, neural crest, placodes) and fates. The many disparate cell migratory behaviors exhibited by these mesenchymal populations have only recently been revealed, necessitating a reappraisal of how these different populations come together to form specific tissues and organs. The objectives of this review are to characterize the diverse migratory behaviors of craniofacial mesenchymal subpopulations, to define the interactions necessary for their assembly into tissues, and to discuss these data in the context of recent discoveries concerning the molecular basis of craniofacial development. The application of antibodies that recognize features unique to migrating neural crest cells has verified the results of previous transplantation experiments in birds and shown the migratory pathways in murine embryos to be similar. Within paraxial or prechordal mesoderm arise myoblasts that are precursors of craniofacial voluntary muscles. These cells migrate, usually en masse, to the sites where overt muscle differentiation occurs. Whereas the initial alignment of primary myotubes presages the fiber orientation seen in the adult, the time at which individual myotubes appear relative to the formation of discrete, individual muscle bundles and attachments with connective tissues varies with each muscle. The pattern of primary myotube alignment is determined by local connective tissue-forming mesenchyme and is independent of the source of myoblasts. Also found within paraxial and lateral mesodermal tissues are endothelial precursors (angioblasts). Some of these aggregate in situ, forming vesicles that coalesce with ingrowing endothelial cords. Others are highly invasive, moving in all directions and infiltrating tissues such as the neural crest, which lacks endogenous angioblasts. The patterns of initial blood vessel formation in the head are also determined by local connective tissue-forming mesenchyme and are independent of the origin of endothelial cells. Neural crest cells, which constitute the predominant connective tissue-forming mesenchyme in the facial, oral, and branchial regions of the head, acquire a regional identity while still part of the neural epithelium, and carry this with them as they move into the mandibular, hyoid, and branchial arches. Some of these regionally unique propensities correspond spatially to genetic and cellular patterns unique to rhombomeres, although the links between gene expression and crest population phenotypes are not yet known. In contrast, the inherent spatial programming of those crest cells that populate the maxillary and frontonasal regions is altered by their proximity to the prosencephalon.