Attention deficit hyperactivity disorder (ADHD) has a growing incidence and prevalence in the United States and throughout the world, much of which is contributed to increased awareness of the condition and solidified diagnostic criteria. Substance use disorder (SUD) similarly has seen a sharp increase, particularly with the rising cases of opioid abuse. Management of ADHD is done primarily with pharmacologic therapy, often stimulants and with psychosocial interventions (i.e., exercise, meditation, peer-to-peer intervention, etc.) for adjunctive management. Management of SUD involves cessation and treatment based on the underlying drug of abuse. Many clinicians are uncomfortable treating ADHD in patients with SUD based on concerns the intervention may lead to an adverse event, including drug relapse, and the development of other psychiatric comorbidities. Concerns also arise about stimulants acting as a gateway drug in adolescents leading to the onset of SUD. Thus, in this narrative review, we aim to shed light on ADHD in relation to SUD and to provide clinical insight based on the current scientific literature on the topic. ADHD causes lesions in subcortical structures in the basal ganglia and limbic system. Treatment of ADHD with stimulants has been shown to normalize malformed neuroanatomical variations and lead to improved long-term outcomes compared to nontreatment of ADHD. Based on current scientific literature, it is recommended to treat ADHD with guidelinedirected pharmacologic agents including stimulants along with non-pharmacologic interventions primarily exercise. There may be some improvement in reducing risky behavior, such as substance abuse, and may even help prevent the development of SUD.