Approximately 2% of identifiable unique chemicals registered under REACH are considered to meet the PMT/vPvM criteria (259 out of 13405 unique, identifiable chemicals registered under REACH); however, the true number is likely higher due to data gaps related to persistent, mobility or toxicity, with a potential maximum of 28% of REACH registered substances (3677 out of 13405 substances) . Developing and applying substance grouping strategies is one way to potentially identify and manage PMT/vPvM substances more effectively. There are two main motivations for a substance grouping approach. The first is to expedite hazard assessments related to the large number of substances being introduced to the global chemical market. The second is to avoid regrettable substitution caused by drop-in substitution , where one substance is replaced by another with similar hazardous properties and effects . Thus, this paper aims to explore how grouping strategies can be generally developed and used to identify, assess and manage new, emerging and well-known PMT/vPvM substances. To provide context, the paper first provides an overview of PMT/vPvM substances, including scoping the numbers of substances covered by existing definitions, reviewing previous successful grouping strategies, and determining the relevance of grouping strategies in the context of PMT/vPvM substances while exploring the future efforts required to achieve this effectively. The principle aim of this article is not specifically targeting the ECHA technical guidance for PMT/vPvM substance assessment, but rather it is on how grouping strategies can be used to screen, assess, regulate and manage groups of PMT/vPvM substances more efficiently.