Spinal cord injury is frequently followed by the loss of supraspinal control of sensory, autonomic and motor functions at the sublesional level. In order to enhance recovery in spinal cord-injured patients, we have developed three fundamental strategies in experimental models. These strategies define in turn three chronological levels of postlesional intervention in the spinal cord. Neuroprotection soon after injury using pharmacological tools to reduce the progressive secondary injury processes that follow during the first week after the initial lesion. This strategy was conducted up to clinical trials, showing that a pharmacological therapy can reduce the permanent neurological deficit that usually follows an acute injury of the central nervous system (CNS). A second strategy, which is initiated not long after the lesion, aims at promoting axonal regeneration by acting on the main barrier to regeneration of lesioned axons: the glial scar. Finally a mid-term substitutive strategy is the management of the sublesional spinal cord by sensorimotor stimulation and/or supply of missing key afferents, such as monoaminergic systems. These three strategies are reviewed. Only a combination of these different approaches will be able to provide an optimal basis for potential therapeutic interventions directed to functional recovery after spinal cord injury.