ABSTRACT Dramatic successes in identifying vertebrate homeobox genes closely related to their insect relatives have led to the recognition of classes within the homeodomain superfamily. To what extent are the homeodomain protein classes dedicated to specific functions during development? Although information on vertebrate gene functions is limited, existing evidence from mice and nematodes clearly supports conservation of function for the Hox genes. Less compelling, but still remarkable, is the conservation of other homeobox gene classes and of regulators of homeotic gene expression and function. It is too soon to say whether the cases of conservation are unique and exceptional, or the beginning of a profoundly unified view of gene regulation in animal development. In any case, new questions are raised by the data: how can the differences between mammals and insects be compatible with conservation of homeobox gene function? Did the evolution of animal form involve a proliferation of new homeodomain proteins, new modes of regulation of existing gene types, or new relationships with target genes, or is evolutionary change largely the province of other classes of genes? In this review, we summarize what is known about conservation of homeobox gene function.