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Background: Adolescents are a unique population with significant unmet health needs. They are often excluded from research that may benefit them as they are perceived as vulnerable and needing protection from research participation. For Research Ethics Committees, conflicting positions in statutes, regulations and ethical guidelines about who provides informed consent for adolescent involvement in health research can be a significant barrier to approving adolescent research. For researchers, the requirement for parental/guardian proxy consent or prolonged approval processes may potentially result in the exclusion of those adolescents most vulnerable and at risk, particularly if issues such as gender-based violence, gender identity, sexuality and sexual practices are in question., Objectives: To describe the challenges to adolescent research and suggest strategies to address these., Method: We consider the legal and ethical framework in South Africa regarding the consenting age for adolescents in research, outline the challenges and, using examples of best practices, suggest strategies to address the current conundrum., Results: We suggest three principles to guide Research Ethics Committees on their approach to reviewing health research involving adolescents. Strategies to develop ethically acceptable approaches to adolescent research and consent processes are described, which include community involvement. We elaborate on examples of nuanced approaches to adolescent research., Conclusion: The inclusion of adolescents in research is critical in informing appropriate and effective health services for this vulnerable population, whilst providing an opportunity to link them into care and services where relevant., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)