Background. Over the past decades there have been tremendous efforts to improve the ethical conduct of research involving humans throughout the world. As a one-size-fits-all philosophy can no longer work, most countries have developed specific legal and ethical guidelines for research, tailored to their own context. We reviewed South African ethical guidelines and Health Research Acts as they pertain to the role of caregivers in consent practices for minors’ participation in HIV/AIDS-related research. Methods. An argument-driven review was conducted on two (...) SA Acts and Guidelines respectively: the SA National Health Act of 2003; the Children’s Act No. 38 of 2005 and the Department of Health Ethics in Health Research Guidelines 2nd edition of 2015 and the Good Clinical Practice Guidelines of 2006, with a particular focus on minors as research participants. We also examined the relevant ethical and legal guidance using an exemplar of paediatric HIV testing within research conducted in SA. Results. Available ethical guidelines for caregivers’ consent in research involving minors are still not comprehensive or aligned with SA regulations governing research with minors. The recent revision and development of the National Health Research Ethics Guidelines, regarding the role of caregivers in consent practice for minors’ participation in health research, may be a positive move in clarifying the proper role for caregivers when enrolling minors in research. Conclusion. Caregivers are deemed to have a role to play in research involving minors. Therefore, the inconsistencies in existing ethical guidelines and governing regulations regarding the role of caregivers in paediatric HIV research, need to be addressed following the recent ethical paradigm change. (shrink)