As advances in cancer therapy have significantly improved mortality rates, there is increasing emphasis on improving quality of life for cancer survivors. One such area of focus is in maintaining fertility, as both chemotherapy and radiation therapy carry significant risks of causing infertility through various mechanisms of gonadal injury. Although fertility preservation options exist, such as sperm or egg banking, they are not always available or indicated for all patients. Fertoprotective agents are proposed substances that may serve to protect the gonad from the harmful impacts of cancer therapy to maintain fertility. However, caution must be taken to evaluate whether these agents could act similarly to protect the tumor from anticancer therapies. In this narrative review, we first describe the various mechanisms by which chemotherapy or radiation therapy can cause gonadal harm. We then review the available research on fertoprotective agents and their proposed mechanisms of gonadal protection. Finally, we discuss what evidence exists for interaction with cancer therapy for each agent, with an emphasis on opportunities for future research. (F S Rev
2025;6:100087. 2025 by American Society for Reproductive Medicine.)