Intervention research with youths at elevated risk for suicidal behavior and suicide--a vulnerable and high risk population--presents investigators with numerous ethical challenges. This report specifically addresses those challenges involving the informed consent and assent process with parents/guardians and youths. The challenges are delineated in the context of pertinent laws and regulatory requirements, and guidelines are suggested for their practical resolution. These are illustrated with case examples from NIMH-funded intervention trials. Through the sharing of such methodological information, intervention researchers can support each other in conducting ethical research in a manner that does not unduly compromise scientific rigor.