During neurulation, craniofacial structures derived from the first branchial arch are determined to become maxillary, mandibular, and tongue formations. At least four interdependent developmental processes become integrated: (1) allocation of cells into specific lineages (perhaps during gastrulation); (2) regulation of time-dependent differential regulatory and structural gene expressions; (3) positional information resulting in pattern formations; and (4) morphogenesis, histogenesis, and cytodifferentiation. This review highlights progress toward understanding when, where, and how the one-dimensional genetic information encoded within DNA (deoxyribonucleic acid) is sequentially expressed into the embryonic craniofacial complex. Specifically, how might intrinsic autocrine and/or paracrine regulatory factors control the developmental program for early first branchial arch morphogenesis, histogenesis, and cytodifferentiation. Rules learned from normal development should be useful toward advancing the diagnosis, treatment, prognosis, and prevention of congenital craniofacial malformations.