Over the past few years, genes involved in the ontogenesis of tetrapod limbs have been isolated and characterized. Some of the developmental mechanisms responsible for the morphogenesis of these complex structures can now be investigated through a new approach. In addition, these genes can serve as tools to re-evaluate some aspects of the long-standing question of the fin-to-limb transition. Comparative molecular developmental biology is providing new insight into the similarities and differences in the morphologies of these homologous structures.