The role of the immune response in spinal cord injury has become a frequent object of debate. Evidence exists to suggest that autoimmunity following neurotrauma can be either beneficial or detrimental to recovery. The following commentary examines the recent findings indicating that mice lacking mature B- and T-lymphocytes have improved behavioral and histological outcomes following thoracic spinal cord injury. These data, presented in the October issue of Experimental Neurology are discussed within the context of previous findings and differing viewpoints in the field of neuroimmunology. Limitations on the translation of immune modulation therapeutics, and clinical perspectives on their future potential are also examined.