The ingenious work of Riddle et al.1, Tickle2, and others in manipulating limbs in chick embryos provided the basic understanding of limb development. It was such work that defined the terms as well as the role of the apical ectodermal ridge, the progress zone, and the zone of polarizing activity in patterning early limb development. Embryology has moved beyond the primitive understanding of which structures form when, into the molecular realm of developmental biology and genetics. As the signaling pathways for limb differentiation become well understood at a molecular level, morphological anomalies in limbs are seen as patterning errors and offer clues to the role of both genetic and epigenetic effects. Investigators now have more sophisticated tools of molecular genetics, such as microarray chips, which can simultaneously search for abnormalities in the expression of thousands of genes, and techniques that can snip and splice as well as amplify and analyze extremely small quantities of DNA. One of the most revolutionary tools is the “knockout” animal, bred specifically to answer the question “What happens if this particular gene is missing?” With the availability of these molecular genetic tools, and the compilation of the human genome, we now have a good, but not perfect, understanding of what should happen in the normal processes of limb development. Before it can be determined whether there is a genetic cause of a congenital malformation, it is necessary to have a baseline understanding of normal limb development—what starts it, what regulates it, and what stops it. From this understanding, we gain insights into uncontrolled growth, including congenital overgrowth conditions and the dysregulation of growth that causes the malignant tumors that occur throughout life. The interest of pediatric orthopaedic surgeons in these conditions stems from our limited control over the growth, ultimate size, and especially the function of limbs that have been affected by growth abnormalities. Because the scientific process of ascertaining the effect, the interactions, the order of cascading steps, and the feedback mechanisms is so very meticulous, a single scientist or team must focus on only one part of the puzzle. Much has been learned in a very short time and it is impossible to stay abreast of all that is now accepted as scientific fact. This paper delves into the regulation and patterning of limb growth, and in particular, the osteocartilaginous elements in the limb.