AbstractMajor changes in the vertebrate anatomy have preceded the conquest of land by the members of this taxon, and continuous changes in limb shape and use have occurred during the later radiation of tetrapods. While the main, conserved mechanisms of limb development have been discerned over the past century using a combination of classical embryological and molecular methods, only recent advances made it possible to identify and study the regulatory changes that have contributed to the evolution of the tetrapod appendage. These advances include the expansion of the model repertoire from traditional genetic model species to non-conventional ones, a proliferation of predictive mathematical models that describe gene interactions, an explosion in genomic data and the development of high-throughput methodologies. These revolutionary innovations make it possible to identify specific mutations that are behind specific transitions in limb evolution. Also, as we continue to apply them to more and more extant species, we can expect to gain a fine-grained view of this evolutionary transition that has been so consequential for our species as well.