Neurobehavioral problems, such as cognitive deficits, agitation, depression, mania, anxiety, apathy, sleep disturbance, and fatigue are common after traumatic brain injury (TBI). There are increasing evidences that typical profile of structural and neurochemical injury play a role in development of the common neurobehavioral sequelae associated with TBI. Regardless of the mechanisms by which they develop, the neurobehavioral consequences of TBI complicate rehabilitation efforts and are usually associated with functional disabilities. Recent studies demonstrate various classes of pharmacological interventions are available to ameliorate a wide range of symptoms associated with neurobehavioral problems of TBI, yet the quality of the evidence is generally poor. Therefore, well-designed randomized controlled trials in large scale, giving high-quality evidence, are required to develop treatment guidelines. Attention to the pharmacological intervention of the neurobehavioral problems of TBI, addition to the nonpharmacological strategies, can serve a critical role in advancing the rehabilitative process which leads to improved quality of life of the patients with TBI, and decreased social impact.