False positive results have long been the bane of High Throughput Screening (HTS) campaigns. Depending on the compound library tested, the target itself and the assay system employed these have been estimated to account for enrichments of up to 95 % in hit outputs. Many sources of undesirable hits exist whether they be technology artefacts, redox cycling compounds, inhibitors of coupled enzyme systems or any other from a myriad of mechanisms. One strategy to cope has been the development of so called ‘nuisance compound’ sets. Over the past decade numerous pharmaceutical companies acting in isolation, including AstraZeneca, have generated their own versions. Whilst the rationale, composition, source and application of these decks has varied between organisations the end goal has remained constant. Each group has aimed to either minimise the prevalence of undesirable actives by optimising assay design or build bespoke triage cascades capable of identifying them. This presentation details the process by which the AstraZeneca set was established and shows the impact it’s had on drug discovery projects. We explore how it differs from those created by some of our peers and finally introduce a new cross industry and academia initiative called LOCRAP. This Library Of Compounds with Really Annoying Pharmacology (LOCRAP) is a joint collaboration between AstraZeneca, Eli Lilly, Novartis, Pfizer, Broad Institute, NCATS and lead academics in the area Jonathan Baell (Monash University) and Mike Walters (University of Minnesota). By pooling our collective knowledge, the intention is to design and deliver an industry standard collection that will be available to all through a third-party commercial partner. This new set will cover multiple classes of problematic compounds and contain thoroughly validated and well annotated examples. We’ll discuss how this has been achieved and what classes are currently included. We are actively seeking contributors with ideas on compounds to include or to act as beta-testing supporters once the collection is available. Our hope is to make the tools and resources available to large pharmaceutical companies an option for any organisation interested in drug discovery no matter how large or small. From this arises the aspiration to globally improve the quality of assays employed for hit identification and subsequently success rates for discovery campaigns.