Objective: To discuss the role of substance-related and addictive disorders (SRAD) that lead patients with attention-deficit hyperactivity disorder (ADHD) to suicide and homicide.Method: Relevant articles were searched via PubMed using several keywords related to this issue. Most of the articles included in this review were published after 2000. Results: Patients with ADHD often fall into crises of catastrophic life events such as suicide or homicide. SRAD play an important role in leading ADHD patients to such events. Because ADHD is characterized by inattentiveness and impulsivity, any kinds of substances, legal or illegal, can deteriorate ADHD symptoms, leading ADHD patients to such catastrophic events. There are several pathways that connect ADHD with SRAD, which are roughly divided into two ways: internalizing mental disorders and externalizing mental disorders. The former includes depression and anxiety disorders characterized by self-inhibition or withdrawal. The latter typically includes conduct disorder or oppositional defiant disorder, as well as antisocial personality disorder, characterized by aggressive or antisocial behaviors or emotions towards others. These comorbid psychiatric disorders are apt to lead ADHD patients to SRAD, and once these patients suffer from SRAD, risk of catastrophic life events seems to increase due to the irreversibility of their adverse mentality. Comorbid mental disorders with ADHD can act, at least partially, as mediators from ADHD to SRAD. Conclusion: SRAD can be a critical risk factor of suicide and homicide among patients with ADHD. Early interventions for families with ADHD and psychiatric comorbidities may work as effective preventive strategies against such events.