In vertebrates, the facial skeleton is derived from cranial neural crest-derived cells and the head paraxial mesoderm. The transcription factor Sox9 is a key regulator of cartilage differentiation, and the Forkhead domain (Fox) family of transcription factors has also been implicated in craniofacial development in mammals, with earlier work suggesting that they might constitute a spatial code for facial skeletal development. Here, Gage Crump and colleagues provide a detailed analysis of the roles of different Fox family members in zebrafish. They first investigate the expression patterns of different Fox genes, focussing particularly on the Fox-C and Fox-F classes and their regulation by different signalling pathways. Then, through individual and combinatorial knockouts, they provide evidence that Fox-C proteins are required for upper facial cartilage formation, while Fox-F proteins regulate midline cartilage and tooth development. In both cases, the Fox factors appear to promote expression of Sox9 targets, perhaps indicating that Fox proteins and Sox9 might co-regulate these loci. Although the significant redundancy between Fox factors complicates analysis of their activities, the similarity between the fish phenotypes and previous reports in mouse suggests conserved functions of Fox family members in craniofacial development across vertebrates.