Objective: This review explores the relationship between ADHD and substance use disorder (SUD), factors that determine the abuse potential of psychostimulants, and strategies for identifying and treating at-risk ADHD patients. Method: This study uses a Medline review of literature. Results: Psychostimulants, such as methylphenidate and amphetamines, are effective first-line pharmacotherapy for ADHD and when used appropriately in individuals with ADHD do not appear to be frequently abused by patients. Diversion and misuse of prescription stimulants are growing concerns, especially among young adults and college students. Short-acting psychostimulant formulations may have higher potential for abuse, misuse, and diversion, but more data are needed to substantiate this observation. Nonstimulant treatments for ADHD may be considered for patients at particularly high risk for substance use, misuse, or diversion of stimulants. Conclusion: In treating patients with ADHD and comorbid substance use, psychostimulants may be a useful pharmacologic alternative. However, the risks of such treatment with high-risk populations must be considered alongside potential benefits. (Contains 2 tables and 3 figures.)