For the first time in the history of neuroscience, hearing allows to systematically investigate brain development with and without sensory experience in humans.This is given by the clinical success of the cochlear implant, a neuroprosthesis that can replace the non-functional inner ear. In recent years auditory neuroscience investigated the neuronal mechanisms of learning, sensitive developmental periods and cross-modal reorganization in parallel in humans and animal models, with highly consistent outcomes. We learned that the brain undergoes a complex adaptation to deafness, both within and outside of the auditory system. These adaptations reorganize the brain optimally to cope with deafness, but they negatively interfere with a later prosthetic therapy of hearing.They eventually close the sensitive developmental periods. The critical nature of sensitive periods is not only a consequence of a developmentally-reduced synaptic plasticity. It is due to the consequences of changes in central integrative functions and cognitive adaptations to deafness.