Neuroplasticity following bilateral deafness and auditory restoration has been repeatedly investigated. In clinical practice, however, a significant number of patients present a severe-to-profound unilateral hearing loss (UHL). To date, less is known about the neuroplasticity following monaural hearing deprivation and auditory input restoration. This article provides an overview of the current research insights on the impact of UHL on the brain and the effect of auditory input restoration with a cochlear implant (CI). An exhaustive systematic review of the literature was performed selecting 38 studies that apply different neural analyses techniques. The main results show that the hearing ear becomes functionally dominant after monaural deprivation, reshaping the lateralization of the neural network for auditory processing, a process that can be considered to influence auditory restoration. Furthermore, animal models predict that the onset time of UHL impacts auditory restoration. Hence, the results seem to advocate for early restoration of UHL, although further research is required to disambiguate the effects of duration and onset of UHL on auditory restoration and on structural neuroplasticity following UHL deprivation and restoration. Ongoing developments on CI devices compatible with Magnetic Resonance Imaging (MRI) examinations will provide a unique opportunity to investigate structural and functional neuroplasticity following CI restoration more directly.