Neural crest cells represent a unique link between axial and peripheral regions of the developing vertebrate head. Although their fates are well catalogued, the issue of their role in spatial organization is less certain. Recent data, particularly on patterns of expression of Hox genes in the hindbrain and crest cells, have raised anew the debate whether a segmental arrangement is the basis for positional specification of craniofacial epithelial and mesenchymal tissues or is but one manifestation of underlying spatial programming processes. The mechanisms of positional specification of sensory neurons derived from the neural crest and placodes are unknown. This review examines the spatial organization of cells and tissues that develop in proximity to sensory neurons; some of these tissues share a common ancestry, others are targets of cranial sensory and motor nerves. All share the necessity of acquiring and expressing site-specific properties in a functionally integrated manner. This integration occurs in part by coordinating patterns of cell migration, as occurs between migrating crest cells and branchial arch myoblasts. Constant rostro-caudal relations are maintained among these precursors as they move dorsoventrally from the hindbrain–paraxial regions to establish branchial arches. During this period the interactions among these and other mesenchymal cells are hierarchical; each cell population differentially integrates its past with cues emanating from new microenvironments. Analyses of tissue interactions indicate that neural crest cells play a dominant role in this scenario. © 1993 John Wiley & Sons, Inc.