The purpose of the current paper was to conduct a systematic review of the literature on predictors of emotional distress in caregivers of persons with traumatic brain injury (TBI), and to provide evidence-based classification for prognostic variables to guide future research and clinical practice. A search was conducted using PubMed, CINAHL and PsycINFO databases. The citations of resulting articles were also reviewed. Twenty-eight articles met inclusion criteria and were retained for review. Reviews were conducted in accordance with the 2011 edition of the American Academy of Neurology (AAN) Guidelines for classifying evidence for prognostic studies. Data abstraction revealed one Class I study, four Class II studies, eight Class III studies, and 15 Class IV studies. Results of the review indicated that caregivers’ report of neurobehavioural problems in the person with injury is a probable predictor of emotional distress for caregivers of persons with complicated mild, moderate or severe TBI (Class B evidence). The level of participation in the person with injury, level of support needed by the person with injury, and family systems functioning are probably predictors of emotional distress for caregivers of persons with severe TBI (Class B evidence). Executive functioning impairment in the person with injury, pre-injury emotional distress in caregivers, caregiver age, caregivers’ use of emotion-focused coping, and social support may possibly be risk factors for caregivers’ emotional distress (Class C evidence). Recommendations for future research and implications for assessment and treatment of family caregivers are discussed.