There is a diverse literature that explores the relationship between youth, music, and mental health, with few attempts at systematic synthesis. This critical interpretive review included 33 studies published between 2000 and 2012 investigating the relationship between music and the mental health of young people, particularly targeting depression. An iterative methodology was used involving several layers of inductive analysis with the intention of generating an organizing framework that critically synthesized the available literature. The organizing framework highlights that decisions related to research design, assessment of health, and the nature of musical engagement have predictably influenced study outcomes. Studies have been limited by the collection of insufficient detail about the full range of individual’s musical behaviors. In addition, there has been inadequate triangulation of health outcomes solicited from a variety of perspectives. More comprehensive research is needed that avoids simplistic dichotomies in relation to music and youth mental health.