The high prevalence of complementary and alternative medicine use including natural health products (NHPs) in the pediatric oncology population is well established. The potential for concurrent use of NHPs with conventional chemotherapy necessitates physician awareness regarding the potential risks and benefits that might come from this coadministration. Knowledge of interactions between NHPs and chemotherapy is poorly characterized; however, an understanding of potential mechanisms of interaction by researchers and clinicians is important. Concerns regarding the use of antioxidants during chemotherapy are controversial and evidence exists to support both adherents and detractors in this debate. Our review addresses issues regarding potential interactions between NHPs and chemotherapies used in pediatric oncology from a pharmacokinetic and pharmacodynamic perspective. Examples of combinations of NHP and chemotherapies are briefly presented in addition to a strategy to avoid (or induce) a possible interaction between a NHP and chemotherapy. In conclusion, more clinical research is needed to substantiate or preclude the use of NHPs in the treatment of cancer and especially in combination with chemotherapy.