Today's youth face unprecedented global challenges to their well-being and cognitive development. Many live in poverty without access to proper nutrition, health care, or education. This chapter describes challenges associated with the assessment of children's mental health and functioning, and identifies risk and protective factors, best practices for prevention, and promising interventions that can be utilized in resource-poor settings. The development of mental health disorders in youth is multifactorial; risk and protective factors for mental health cross biological, psychological, and social domains. Substantive research and resources have been dedicated to understanding and ameliorating mental health service provision among children and adolescents in high-income countries, and thus effective evidence-based treatments for most mental health disorders exist. The tenets of the interventions framework of SAFE (Safety and security, Access to health care, Family and others support, and Education) have useful application to all children facing adverse and difficult life situations.