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Progress in biomedical technology (cochlear, vestibular, and retinal implants) has led to remarkable success in neurosensory restoration, particularly in the auditory system. However, outcomes vary considerably, even after accounting for comorbidity—for example, after cochlear implantation, some deaf children develop spoken language skills approaching those of their hearing peers, whereas other children fail to do so. Here, we review evidence that auditory deprivation has widespread effects on brain development, affecting the capacity to process information beyond the auditory system. After sensory loss and deafness, the brain's effective connectivity is altered within the auditory system, between sensory systems, and between the auditory system and centres serving higher order neurocognitive functions. As a result, congenital sensory loss could be thought of as a connectome disease, with interindividual variability in the brain's adaptation to sensory loss underpinning much of the observed variation in outcome of cochlear implantation. Different executive functions, sequential processing, and concept formation are at particular risk in deaf children. A battery of clinical tests can allow early identification of neurocognitive risk factors. Intervention strategies that address these impairments with a personalised approach, taking interindividual variations into account, will further improve outcomes.