Cross-education describes the strength gain in the opposite, untrained limb following a unilateral strength training program. Since its discovery in 1894, several studies now confirm the existence of cross-education in contexts that involve voluntary dynamic contractions, eccentric contraction, electrical stimulation, whole-body vibration and, more recently, following mirror feedback training. Although many aspects of cross-education have been established, the mediating neural mechanisms remain unclear. Overall, the findings of this review show that the neural adaptations to cross-education of muscle strength most likely represent a continuum of change within the central nervous system that involves both structural and functional changes within cortical motor and non-motor regions. Such changes are likely to be the result of more subtle changes along the entire neuroaxis which include, increased corticospinal excitability, reduced cortical inhibition, reduced interhemispheric inhibition, changes in voluntary activation and new regions of cortical activation. However, there is a need to widen the breadth of research by employing several neurophysiological techniques (together) to better understand the potential mechanisms mediating cross-education. This fundamental step is required in order to better prescribe targeted and effective guidelines for the clinical practice of cross-education. There is a need to determine whether similar cortical responses also occur in clinical populations where, perhaps, the benefits of cross-education could be best observed.