Over the past six decades, clinical scientists have conducted more than 800 randomized controlled trials of psychotherapies for children and adolescents. We have learned a lot from these studies about what predicts successful therapy with young people. Findings indicate that evidence-based psychotherapies are more effective than usual clinical care; that youth psychotherapy is most successful with anxiety disorders and least successful with depression; and that youth psychotherapy does not need to be lengthy or complicated to be effective—brief, simple therapies can be quite helpful. Research has also shown that therapy does not have to be done in-person, by a professional therapist, or even by a human being to be beneficial—even digital interventions delivered remotely can be effective. Studies have also shown that outcomes of therapy with young people can differ depending on the society in which the young people live: treatment outcomes are worse for girls or black youths in sexist or racist environments. There are also some surprises: Youth psychotherapies developed in high income countries are actually much more effective when they are delivered in low and middle income countries; and, inexplicably, although psychotherapy is generally effective with young people, the magnitude of benefit from therapy has not grown any larger across six decades of research. These surprising findings raise important questions and a major challenge for the future.