The evolution of the frontal appendage is an important event for the early arthropods to improve their feeling and feeding ability under the fiercely ‘arm race’ press in Cambrian explosion. The results from paleontology and development biology indicate that the ground pattern of frontal appendages of arthropods is stout antennae with low number of homologous articles, which evolve to long, flagelliform antenna and even leg like “great appendage” with less number of articles, as found in fossil trilobites and so called “great appendage” arthropods respectively. The great appendages with a proximal arm and distal claw like structure represent most likely the plesiomorphic state of the cheliphore of the Chelicerata. Therefore, the great appendage arthropods may be the stem groups of the Chelicerata. In this article, the authors discuss the possible genetic basis of the origin of great appendages. It is possible that Hox genes or other developmental regulatory molecules involve in changing the special interaction of Dll, dac and hth in the development of the frontal appendages, thereby lead to the appendage primordia acquire the limb specific development program.