Vertebrate limbs display three obvious axes of asymmetry. These three axes are referred to as proximal-distal (Pr-D; shoulder to digit tips), anterior-posterior (A-P; thumb to little finger), and dorsal-ventral (D-V; back of hand to palm). At a molecular level, it is now possible to define the signals that control patterning of each of the three axes of the developing limb. These signals do not work in isolation though but rather their activity must be integrated such that the various limb elements are coordinately formed with relation to these three axes. This review will provide an overview of the intricate medley amongst the molecular signals that serve to establish and coordinate patterning information along the three primary axes of the limb.