Increasing numbers of adults and children around the world are using natural health products (NHPs) to promote wellbeing or alleviate illness. Although often considered safe due to their natural origin, NHPs are potentially pharmacologically active and, therefore may cause harm. Limited data suggest that NHPs can interact with other NHPs as well as with prescription medication and foods. Although some common NHP-drug interactions have been identified and studied, in general, the epidemiology of NHP-drug interactions is not well-understood, in part because these harms are often underreported. Users rarely disclose NHP use to their physicians, and physicians rarely enquire about such use. Even if physicians become aware of a potential NHP-drug interaction, passive surveillance systems mean that it is left to the physicians discretion whether or not to report it to the proper authority. It is likely that active surveillance of NHP-drug interactions would result in increased reporting of NHP-related harms as well as better quality reports. Subsequent lab investigation would determine if adulteration, contamination, species misidentification, or misuse was responsible for the harm, or if a pharmacokinetic or pharmacodynamic NHP-drug interaction occurred. This kind of thorough detection and investigation of potential NHP-drug interactions is necessary to ensure the safe use of NHPs.