AbstractHistorically, the appearance of new psychoactive materials (and hence the requirement for new reference standards) has been relatively slow. This position has now changed, with 101 new psychoactive substances reported to EMCDDA‐Europol since 2006. The newly reported materials, and associated metabolites, require properly certified reference materials to permit reliable identification and quantification.The traditional approach and timescales of reference material production and certification are being increasingly challenged by the appearance of these new substances. Reference material suppliers have to adopt new strategies to meet the needs of laboratories. This situation is particularly challenging for toxicology standards as the metabolism of many of these substances is initially unknown.Reference material production often involves synthesis from first principles. While it is possible to synthesis these materials, there can be significant difficulties, from synthetic complexities through to the need to use controlled materials. These issues are examined through a discussion of the synthesis of cathinones. Use of alternative sources, including pharmaceutical impurity materials or internet sourced products, as starting materials for conversion into appropriately certified reference materials are also discussed.The sudden appearance and sometimes brief lifetime in the market place of many of these novel legal highs or research chemicals present commercial difficulties for reference material producers. The need for collaboration at all levels is highlighted as essential to rapid identification of requirements for new reference materials. National or international commissioning or support may also be required to permit reference material producers to recover their development costs. Copyright © 2011 John Wiley & Sons, Ltd.