The study of comorbidity between substance use disorders (SUD) and attention-deficit hyperactivity disorder (ADHD) is relevant to both research and clinical practice in developmental pediatrics, psychology, and psychiatry, with implications for diagnosis, prognosis, treatment, and health care delivery. This chapter reviews data relevant to understanding the overlap between ADHD and SUD with an emphasis on tangible factors mediating this association. ADHD without comorbidity appears to confer an intermediate risk factor for SUD that is manifested in young adults/ college-aged students. Patients with ADHD and SUD require multimodal intervention incorporating addiction and mental health treatment. Pharmacotherapy in ADHD and SUD individuals needs to take into consideration abuse liability, potential drug interactions, and compliance concerns. Given the prevalence and major morbidity and impairment caused by SUD and ADHD, prevention and treatment strategies for these patients need be further developed and evaluated.