This study was aimed at examining the relationship between suicidal attempts, polydrug use, and depression in adolescents. A sample of 691 adolescents and their parents were interviewed. Subjects who met the criteria for depression and those who used alcohol were significantly more likely to be suicidal attempters (OR = 6.8, p < 0.001; OR = 7.5, p < 0.001). Polydrug users were significantly more likely to attempt suicide (OR = 8.8, p = 0.032). Adolescents with mothers who met the criteria for depression were more likely to report suicide attempts (OR = 2.4, p = 0.069). Health professionals need to screen for polydrug use and depression to prevent future suicidal behaviors.