This chapter examines the coordinate system that the genome uses to make the legs of humans and flies and explores the extent to which the gene circuitry is similar in these two cases. As with many other organs and organ systems the underlying circuitry is quite similar indeed. Along the anterior-posterior axis, for example, the same signaling molecule (Hedgehog) acts as a morphogen to inform cells of their location along the axis. Along the proximal-distal (base to tip) axis, the legs of both humans and flies employ the same transcription factors to demarcate three subdivisions. One of those factors, Distal-less has long been thought to control the outgrowth of appendages from phyla across the entire animal spectrum. While this may be true, the original function of that factor seems to have been in the nervous system, rather than in the limbs. We have no idea why the genome would assign a neural specification gene an appendage task, but such a weird destiny has not just happened with Distal-less, but also with Engrailed. Many other mysteries of limb evo-devo are presented, including two weird syndromes that cause extra joints in the distal parts of human and fly appendages.