The vertebrate head is a highly complex composite structure whose morphological characteristics are controlled at the level of the gene. There is now increasing evidence for the role of gene families that encode transcription factors in determining the embryonic plan of the developing craniofacial complex. These genes act as regulators of gene transcription being intimately involved with the control of complex interactions between multiple downstream genes. Combinatorial expression of the Hox genes (a family of highly conserved master regulatory genes related to the homeotic genes of the fruitfly Drosophila) have been shown to play a definitive role in patterning distinct regions of the craniofacial complex. In the vertebrate, Hox genes pattern the hindbrain and branchial regions of the developing head up to and including structures derived from the second branchial arch. The first branchial arch and more rostral regions of the head are patterned by groups of homeobox genes more diverged from the original Hox clusters. Transgenic mice, with targeted disruptions in many of these genes, are now providing insights into the molecular mechanisms that lie behind a number of craniofacial defects seen in man.