This chapter discusses current knowledge of how precisely ordered afferent synaptogenesis occurs during development. It also explains the potential for reforming functional circuits by correct rewiring during regeneration. Most of the knowledge of the mechanisms involved in establishing circuits between distant central nervous system (CNS) neuronal populations comes from studies of the axonal projection from the eye to central brain targets. The output neurons of the eye are the retinal ganglion cells (RGCs), whose axons exit the eye as the optic nerve, cross the midline at the optic chiasm, and innervate central brain structures. RGCs in fish and frogs survive optic nerve lesion and sprout new axonal extensions that correctly navigate to the tectum, reform the retinotectal map, and demonstrate visual responsivity. Regeneration recapitulates a critical period of heightened plasticity during which activity-dependent mechanisms mediate map refinement through pruning of ectopic axonal branches.