Despite growing national concern, the US remains ill equipped to meet the escalating crisis of youth suicide. Suicide is now the second leading cause of death among youths, yet the infrastructure for prevention research lags behind. Funding remains limited, high-quality trials are rare, and suicide prevention in clinical practice is constrained by methodological and ethical challenges. Research on treatments for suicidal thoughts and behaviors among young people faces several inherent challenges. Suicide-related outcomes are rare, requiring large sample sizes and long follow-up periods, making randomized clinical trials particularly difficult and expensive. There are inherent ethical challenges in using standardized “treatment-as-usual” comparison groups in intervention studies, due to the imperative to ensure all participants, especially those at risk for suicide, receive a minimum standard of care that often includes active therapeutic components. Compounding these challenges is the absence of comprehensive, unified guidelines for addressing suicide risk, including reducing access to lethal means across pediatric primary care, emergency departments, and specialty mental health settings. This variability in clinical practice complicates implementation research and makes it harder to generate actionable, generalizable evidence.