Evidence suggests a significant association between use of psychoactive substances among adolescents and suicidal behavior among adolescents during the past two decades. Accumulating evidence, although not unanimous, supports the hypothesis of psychoactive substance abuse among adolescents as a risk factor for a range of suicidal behavior—ideation, attempted suicide, and completed suicide. With increasing rates of psychoactive substance abuse for the adolescent population during the past 20 years, this appears to be an increasingly important factor. It is not known if the association is causal. Psychoactive substance abuse appears to be associated with a greater frequency and repetitiveness of suicide attempts, more medically lethal attempts, a measured seriousness of intention, and greater suicidal ideation. Additional data support a specific association between alcohol intoxication and suicide by firearms among adolescents. Adolescents who abuse psychoactive substances, particularly those with any type of depressive disorder, appear to be at higher risk for suicidal behavior and may need appropriate psychiatric treatment.