The aim of this paper was to systematically review the research published in English language on the effectiveness of drugs for the treatment of neurobehavioural disorders in patients with traumatic brain injury (TBI). A literature search using Medline, Pre-Medline, Embase, Psychlit and Cochrane Library databases between 1990 and January 2003 as well as a hand search of Brain Injury since 1996 were carried out. Phrases such as 'head injury', 'brain injury', 'drug treatment', 'drug trials' and 'randomized controlled trials' were used. Sixty-three papers were selected for data synthesis. Of these, 13 were randomized controlled trials, eight were prospective observational studies, four were retrospective studies, 25 were case series and 13 were single case studies. There was a dearth of type I-III evidence. There was no strong evidence either way to suggest that drugs are effective in the treatment of behaviour disorders in patients with TBI. However, there was weak evidence, primarily based on case studies that psychostimulants are effective in the treatment of apathy, inattention and slowness; high dose beta-blockers in the treatment of agitation and aggression; anti-convulsants and anti-depressants (particularly SSRIs) in the treatment of agitation and aggression, particularly in the context of an affective disorder; and possibly a specific neuroleptic methotrimeprazine in the treatment of agitation in the post-acute stage of Acquired Brain Injury. Some drugs that are effective in some patients have been shown to be ineffective in others. Some drugs, particularly lithium and dopaminergic drugs could cause adverse effects and deterioration in some patients.