This study investigated the relation between symptoms and a variety of health-related risk-taking behaviors during adolescence. A survey of 20,745 adolescents from the National Longitudinal Study of Adolescent Health provided data for analysis. Adolescents who reported more depressive symptoms were found to wear seatbelts less often, wear bike-helmets less often, and drive while drunk more frequently. Depressive symptoms did not correlate with reported condom use. The found relations were all mediated by reported levels of hopelessness. Reported levels of anhedonia and suicidality also mediated some of the found relations. Therefore, adolescents experiencing depressive symptoms, especially those reporting hopelessness, should be considered at jeopardy for a variety of health-related risk-taking behaviors.