Traumatic brain injury (TBI) is a significant public health problem that affects millions of people annually in the USA. Neuropsychiatric symptoms such as cognitive deficits, depression, mania, anxiety, psychosis, apathy, and sleep disturbance are common after TBI. An extensive array of pharmacological options are available to treat a wide range of neuropsychiatric sequelae of TBI, yet there have been few controlled clinical trials to assess the effects of pharmacotherapy in TBI patients. Treatment of the neuropsychiatric disturbances associated with TBI should result in decreased handicap, improved quality of life, and decreased societal impact. There is a dire need for large, randomized, double blind, placebo-controlled trials that include a broad range of cognitive and behavioral outcome measures.