"No health without mental health" has become a rallying call for the World Health Organization and numerous service providers, training institutions, health researchers, and advocacy groups around the world. It is timely to consider the implications of this call for South Africa. We review key evidence regarding the burden and risk factors for mental disorders in South Africa and crucial challenges for local mental health services and research. We emphasize that mental disorders are more impairing but less treated than physical disorders, and that existing services need to be scaled up and adapted to the local context. New research is needed to determine what interventions work best in the South African context.