Designing a randomized controlled trial (RCT) to identify the efficacy of treatments for suicidal youths is challenging and requires great care. The lack of a comprehensive treatment evidence base for suicidal youths is largely the result of the complexity of these youths and the many impediments to mounting a RCT for the commonly used treatments-medication and psychotherapy. Correctly choosing the hypothesis to be tested, the appropriate sampling frame, the intervention and control groups, and the outcome variables increases the likelihood that the study will be feasible, ethical and clinically meaningful. To meet these goals, the sampling frame needs to be broad, but not require overly complex assessment, treatment and rescue protocols; intervention and control groups must meet or beat the 'standard of care', and be acceptable to participants and clinicians. The outcome variables need to be measurable, sensitive to change and common enough to identify between group differences without large samples. This manuscript: (1) reviews existing studies of interventions for suicidal youths, (2) describes challenges in selecting the population, treatment and control conditions, and appropriate and meaningful outcome measures, and (3) discusses alternative methodological approaches that may be necessary to address the complex treatment needs of suicidal youth.