Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Accidents are a major cause of brain injury, and many accidents are alcohol or drug related. Evidence indicates that a vast majority of victims test positive for alcohol or illicit drugs at the time of hospital admission. Research also suggests that a majority of TBI survivors were moderate to heavy drinkers pre-injury. This manuscript reviews literature on pre- and post-injury substance use patterns, abuse risk factors, and dangers of post-injury use. Assessment is discussed in detail with information provided on the need for quantitative assessment, records review, corroboration, and long-term monitoring. Information is also provided on critical features of treatment, prevention, and education, and on the role of psychologists in substance abuse assessment and treatment. The manuscript concludes with a section addressing issues, questions, and concerns commonly encountered by clinicians.