In response to the question, ‘What is the place of universal, selective and indicated prevention strategies for depression and other mood disorders?’ posed by Hickie et al. (2024), we examine the role of school-based strategies for universal and targeted (including selective and indicated) prevention of depression. Schools represent a unique opportunity for systematic evidence-based depression prevention, targeting key developmental risk periods before peak depression onset. However, the realisation of this potential has been challenging particularly for universal approaches. We summarise the evidence for each of these tiers of prevention, including recent large-scale trials of universal prevention in high-income countries. Targeted approaches show more consistent preventive effects on depression however hold significant implementation challenges in the school context. We provide recommendations about the next steps for the field including a continuum of support across all levels of prevention outlined above and broadening current strategies to focus on the school contexts and structural factors in which prevention programs are delivered, as well as teacher mental health.