The demographics and epidemiology of spinal cord injury (SCI) are well documented . Whether traumatic or occurring as a result of ischaemia, inflammatory demyelination or cervical myelopathy, SCI is a highly complex, multifactorial injury to repair 1 B.H. Dobkin and L.A. Havton, Basic advances and new avenues in therapy of spinal cord injury, Annu. Rev. Med. 55 (2004), pp. 255–282. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (46) and . Promoting regeneration has been a major basic research focus with success shifting dogma from the injured spinal cord as immutable to the potential for functional repair , although considerable hurdles remain in translating findings to humans . Despite identification of cellular and molecular factors promoting axon regeneration experimentally , the link between regeneration and return of function is often unknown, numbers of regenerated axons are small and the distances grown short . However, plasticity and its shaping by physical activity are emerging as major contributors to functional recovery  and . The challenges are to understand the mechanisms underlying activity-dependent plasticity which optimise functional outcome and reduce the incidence of secondary complications after SCI. This review highlights recent research on plasticity following SCI and in other pertinent models to (i) define what spontaneous plasticity is and whether it is useful, (ii) describe how activity drives cellular and molecular plasticity and (iii) specify factors contributing to optimal functional ‘readout’ of activity-dependent plasticity for both cellular function and behavioural outcome.