Non-interventional clinical research projects constitute a significant part of clinical research conducted worldwide, especially in the academic setting. The Swiss law and regulations do not require monitoring to be performed in non-interventional research projects. Nevertheless, applying (risk-based) monitoring procedures in such projects should be considered as part of the risk mitigation strategy. This position paper discusses and provides recommendations regarding the implementation of monitoring strategies for non-interventional human research projects. This includes projects that prospectively collect health-related data and biological samples, as well as “further use” projects that make use of data and samples that were collected for other purposes independently of the research project (e.g., routine clinical data and samples).