Many useful therapeutic approaches are available for those who have experienced brain injury. As has been found with the treatment of psychiatric disorders such as depression, panic disorder, and obsessive-compulsive disorder, a combination of therapeutic interventions administered simultaneously often provides more effective treatment than using a single modality. Individual, cognitive, behavioral, and family therapy, as well as environmental manipulation, all may affect symptoms and the patient's ability to cope with them and are essential elements of any treatment plan for persons with neuropsychiatric disturbances after traumatic brain injury (TBI) (see Chapters 31, 36, 37, 38, and 39). For many patients, pharmacotherapy may be required to provide relief from such symptoms and to facilitate their ability to benefit maximally from nonpharmacological interventions. In this chapter, we first consider neurochemical disturbances produced by TBI in order to frame the review of pharmacological interventions for posttraumatic neuropsychiatric disturbances. Next, the general principles of psychopharmacological management are reviewed. Finally, we describe briefly the medication options for the treatment of the most common neuropsychiatric sequelae of TBI and offer practical guidance for their use in everyday clinical practice. A more detailed description of the role of pharmacotherapy in the treatment of specific neuropsychiatric symptoms or syndromes following TBI is presented in chapters on those subjects elsewhere in this volume.