The most common causes of traumatic brain injury (TBI) are motor vehicle accidents, falls, violence, and sports and recreational activities. Severity of head injury can be determined on the basis of any combination of the following: initial Glasgow Coma Scale (GCS), the duration of loss of consciousness (LOC), and the duration of post traumatic amnesia (PTA). The underlying etio-pathogenesis of post-TBI depression is most likely multi-factorial and most likely involves biopsychosocial factors. This chapter lists out the risk factors for post-TBI depression. Several psychiatric syndromes have been reported in individuals with TBI. These include disturbances of mood, cognition, personality, and behavior. Accurate diagnosis of post-TBI major depression is arduous because a number of symptoms of major depression, particularly the neuropsychiatric symptoms, are directly related to the brain injury itself. The approach to management may follow a biopsychosocial model involving pharmacotherapy, psychotherapy, education, and support for caregivers or family members.