According to Commission Decision (EU) 2017/848 under the Marine Strategy Framework Directive (MSFD), EU Member States (MS) shall consider, in their Descriptor 8 primary criterion (D8C1) assessments, the WFD Priority Substances (PS) and River Basin Specific Pollutants (RBSP) within coastal and territorial waters and also beyond territorial waters if these still may give rise to pollution effects. Some WFD PS might not be relevant for the marine environment in the open sea and, consequently, might be excluded from MSFD monitoring beyond the territorial waters. MS have expressed the need for a framework for the deselection of WFD PS from monitoring under the MSFD, in order to save resources. The European Commission’s Joint Research Centre (JRC), collaborating within the MSFD Expert Network on Contaminants, has developed a pragmatic approach to identify the WFD PS that can be excluded from MSFD monitoring in the open sea beyond territorial waters without reducing protection of European Seas. This should preempt the need for individual MS to provide rationales for such exclusions, support comparable monitoring and assessments across national boundaries, and enable MS to focus their monitoring efforts on other (including emerging) substances that require attention.