This chapter discusses the current understanding of relations between attention deficit hyperactivity disorder (ADHD) and substance use. Children with ADHD are at risk for problems in substance use; evidence suggests that the relations between ADHD and substance use may differ across age groups, gender, and comorbid conditions. Important issues regarding appropriate assessment and developmental trajectories may play a role in how these differences are understood. In comorbid substance use and ADHD, significant overlap in genetic, neurobiological, and trait factors suggests that ADHD and substance use share a common etiology, although factors influencing the phenotypic expression of these factors continue to play an important role in how comorbidity is expressed. Finally, treatment of these comorbid conditions is discussed, both in terms of the issues surrounding medication for ADHD in the context of substance abuse and potential nonmedication treatments that address both substance use and ADHD symptoms through cognitive behavioral strategies.