PRIMARY OBJECTIVE: The purpose of this report is to review both fundamental studies in laboratory animals and preliminary clinical data suggesting that certain drugs may affect behavioural recovery after brain injury. MAIN OUTCOMES AND RESULTS: Laboratory studies show that systemically-administered drugs that affect specific central neurotransmitters including norepinephrine and GABA influence affect recovery in a predictable manner. Although some drugs such as d-amphetamine have the potential to enhance recovery, others such as neuroleptics and other central dopamine receptor antagonists, benzodiazepines and the anti-convulsants phenytoin and phenobarbital may be detrimental. In one study, 72% of patients with traumatic brain injury received one or a combination of the drugs that may impair recovery based on both animal experiments and studies in recovering stroke patients. CONCLUSIONS: Until the true impact of these classes of drugs are better understood, care should be exercised in the use of medications that may interfere with the recovery process in patients with traumatic brain injury. Additional research needs to be completed before the clinical efficacy of drugs that may enhance recovery can be established.