Since 2020, Wellcome has been commissioning research teams from across the world to review the evidence for different approaches that are deemed to help prevent, treat, and manage anxiety and depression in 14 to 24-year-olds globally. We refer to approaches that make a difference as ‘active ingredients’. These active ingredients are the building blocks of what is most likely to make a difference in preventing or addressing youth anxiety and depression. They are varied and connected, spanning biological, cognitive, relational, and societal approaches. In this report, we summarise the key insights gained from the second group of 21 teams we commissioned in 2021, to review the evidence underpinning 19 active ingredients of effective interventions.