Researchers and education leaders have suggested that universal school-based prevention programs could improve youth mental health at a population level, yet recent trials of universal school-based prevention programs (e.g., MYRIAD, CSC) found null or iatrogenic results. In this debate piece, we argue that these results must be contextualized alongside existing knowledge that universal programs are ideally implemented within multitiered systems, promoting student autonomy tends to promote uptake and adherence, and individual trials do not outweigh decades of academic and community expertise. We offer suggestions for moving forward in research on and implementation of universal school-based prevention programs.