Several neurotrophic factors are known to induce neuroprotection in traumatic injuries to the central nervous system (CNS). However, many neurotrophins are unable to attenuate cell death following CNS injuries. New data generated in our laboratory show that a suitable combination of neurotrophic factors may enhance the neuroprotective efficacy of neurotrophins on cell and tissue injury and improve sensory motor functions. This novel aspect of neurotrophins treatment in combination in spinal cord injury (SCI) induced behavioral dysfunctions and spinal cord pathology is examined in a rat model. Our investigations suggest that a suitable combination of neurotrophins will attenuate both neural and non-neural (glial cells and endothelial cells) damage in SCI leading to enhanced neuroprotection. The possible cellular and molecular mechanisms of synergistic effects of some neurotrophins in combination are still speculative and require further investigation.