<p>Potential for harm or non-beneficence in psychological treatments remains understudied compared to questions of benefit or efficacy, especially in youth populations. Further study is critical for upholding the ethical mandate to both maximize salutary outcomes and minimize harm/non-beneficence. In the present special issue, authors of target articles incisively delineate parameters of harm and associated clinical strategies for measuring and addressing it, along with recommendations for research advancing understanding of harm in youth mental health treatment. In this commentary, we synthesize key points across the articles and offer future directions for advancing knowledge on treatment harm. First, we provide historical context that includes the origins of the concept of <i>Primum non nocere,</i> its initial linkages with clinical psychology, and controversies relating to the scientific study of psychotherapy. Second, we leverage lessons learned from the evidence-based treatment movement to advance the study of harm. We suggest that research aimed at advancing understanding harm in youth treatment ought to transpire <i>concurrently</i> with research examining putative benefits of such interventions, including a deliberate focus on mechanisms and moderators of <i>both</i> benefit and harm. Third, we identify several contemporary societal trends relevant to our understanding of harm, including current skepticism of science and proliferation of pseudoscientific interventions. We conclude by discussing implications for furthering knowledge of potential harms in youth mental health treatment across the domains of theory, research, and dissemination. We hope this special issue and commentary stimulate further thought and research in this heretofore understudied area.</p>