Human spinal cord injury (SCI) is a devastating condition that results in persistent motor deficits. Considerable basic and clinical research is directed at attenuating these deficits. Many basic scientists use animal models of SCI to (1) characterize lesion development, (2) determine the role of spared axons in recovery, and (3) develop therapeutic interventions based on these findings. In this article, current research is reviewed that indicates: (1) most individuals with SCI will have some sparing of white matter at the lesion epicenter even when the lesion appears clinically complete, (2) even minimal tissue sparing has a profound impact on segmental systems and recovery of function, and (3) facilitatory intervention such as weight bearing and locomotor training after SCI may be more effective than compensatory strategies at inducing neuroplasticity and motor recovery. Body weight supported treadmill step training is discussed as an example of new facilitatory interventions based on basic science research using animal models.