Traumatic brain injury (TBI) is one of the most common causes of injury and disability, affecting about 1.7 million individuals annually in the U.S. Furthermore, TBI is also recognized as the “signature wound” for military personnel in recent wars. Both civilian and military TBIs result in individual, family, and societal economic and health costs. Even mild TBIs (i.e., concussions) can produce persistent difficulties in mental and physical well-being (e.g., problems with sleep, fatigue, pain, and cognitive functioning), which may be compounded by psychiatric comorbidities. Current treatment and management of the TBI patient typically involves case-by-case use of pharmacologic and/or cognitive-behavioral approaches that individually address post-TBI symptoms. We review the current literature on TBI diagnosis and treatment strategies and note areas where clinical controversies exist. It is hoped that through continued research (and discussion) of these important issues, a greater consensus on the science of treatment of TBI will be achieved.