Axon regeneration has long been studied in vertebrate model organisms and neuronal cultures. Recent development of axon regeneration paradigms in genetic model organisms, such as Caenorhabditis elegans, Drosophila and zebrafish, has opened an exciting field for in vivo functional dissection of regeneration pathways. Studies in these organisms have discovered essential genes and pathways for axon regrowth. The conservation of these genes crossing animal phyla suggests mechanistic relevance to higher organisms. The power of genetic approaches in these organisms makes large-scale genetic and pharmacological screens feasible and can greatly accelerate the mechanistic understanding of axon regeneration.