During the time period following damage, the brain undergoes widespread reorganizational processes. Manipulations of behavioral experience can be potent therapeutic interventions for shaping this reorganization and enhancing long-term functional outcome. Recovery of function is a major concern for survivors of CNS damage, and management of post-injury rehabilitation is increasingly becoming a topic of chief importance. Animal research, which is the focus of this review, suggests that, in the absence of behavioral manipulations, the brain is unlikely to realize its full potential for supporting function. However, experiences also have the capacity to be maladaptive for brain and behavioral function. From a treatment perspective, it may be unwise to adopt the canon of ‘first, do no harm’ since maladaptive experiences include behaviors that individuals learn to do on their own. A better understanding of how behavioral experience interacts with brain reorganization could result in rehabilitative therapies that are individually tailored and optimized for functional outcome.