We do not know the extent to which depression contributes to long-term disability following traumatic brain injury (TBI), although depression is one of several potential psychiatric illnesses that may be common following TBI. Major depression may be triggered by physical or emotional distress, and it can deplete the mental energy and motivation needed for both recovering from the depression itself and adapting to the physical, social, and emotional consequences of trauma with brain injury. Depression may be masked by other deficits after head injury, such as cognitive changes and flat affect, which may be blamed for lack of progress in post-trauma treatment but actually reflect underlying depression. Clinicians, caregivers, and patients lack formal evidence to guide the timing of depression screening, which tools to use for screening and assessment, treatment choices, and assessment of treatment success. Depression is defined by criteria that likely circumscribe a heterogeneous set of illnesses. While no single feature is seen in all depressed patients, common features include sadness, persistent negative thoughts, apathy, lack of energy, cognitive distortions, nihilism, and inability to enjoy normal events in life. Especially in a first episode, individuals and families may not recognize the changes as part of an illness, making identification and self-reporting of the condition challenging. Active screening is essential to recognition, treatment, and prevention of recurrence. Depression reduces quality of life, impairs ability to function in social and work roles, and causes self-doubt and difficulty taking action, all of which can delay recovery from TBI. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, defines the illness in terms of physiologic disturbances of sleep, appetite, attention and concentration, motor activity, and energy, and of psychological losses of interest in normal activities, hope, and self-worth while ruminating with excessive sadness, guilt, and suicidal thoughts. The disturbances may also occur following TBI due to other circumstances, such as pain that disrupts sleep, which may mask the recognition that the sleep disturbance is also a part of a burgeoning depression. The need for systematic evaluation of the prevalence and consequences of depression following TBI is imperative, given the potential for mitigating suicide and unnecessary disability. In preparing this report, we have addressed the following key questions: KQ1. What is the prevalence of depression after traumatic brain injury, and does the area of the brain injured, the severity of the injury, the mechanism or context of injury, or time to recognition of the traumatic brain injury or other patient factors influence the probability of developing clinical depression? KQ2. When should patients who suffer traumatic brain injury be screened for depression, with what tools, and in what setting? KQ3. Among individuals with TBI and depression, what is the prevalence of concomitant psychiatric/behavioral conditions, including anxiety disorders, post-traumatic stress disorder (PTSD), substance abuse, and major psychiatric disorders? KQ4. What are the outcomes (short and long term, including harm) of treatment for depression among traumatic brain injury patients utilizing psychotropic medications, individual/group psychotherapy, neuropsychological rehabilitation, community-based rehabilitation, complementary and alternative medicine, neuromodulation therapies, and other therapies? KQ5. Where head-to-head comparisons are available, which treatment modalities are equivalent or superior with respect to benefits, short- and long-term risks, quality of life, or costs of care? KQ6. Are the short- and long-term outcomes of treatment for depression after TBI modified by individual characteristics, such as age, preexisting mental health status or medical conditions, functional status, and social support?