In 2005, the NIH Molecular Libraries Program (MLP) undertook the first large-scale identification of tool compounds to expand biological insights, now termed small-molecule chemical probes. Their systematic generation against a range of molecular targets was a key driver for the establishment of the PubChem database in order to collate structures and data from the initial ten funded screening centres. The concomitant screening compound collection was established as the Molecular Libraries Small Molecule Repository (MLSMR) for which PubChem had hosted 255,000 compounds by the end of 2005 and since expanded to 406,000 by 2015 (but updates have ceased). Although 25 of the 64 early compounds were judged to be of equivocal quality by a crowdsourcing assessment in 2009 the program progressed to 375 probes (see data section below) before ending in 2014. As conceived from the outset, the availability of these compounds and, crucially, their associated characterisation data, has facilitated the exploration of new targets, pathways and therapeutic hypotheses. Notwithstanding these success stories, the MLP undertaking has been subject to criticisms that remain relevant to contemporary efforts. These include considerations of the MLSMR fitness-for-purpose as a library accrued in an academic context (compared to arguably better-resourced pharmaceutical company screening collections), persistent probe quality issues and remaining confusion on exactly how many probe compounds the program generated. A less tangible but equally important success of the MLP is that, from approximately 2010 onwards, it inspired other organisations to also initiate probe discovery with open dissemination. The three most recent announcements (but not yet surfacing data) are EU-OPENSCREEN with probe development as one of their main objectives, the EUbOPEN 10 consortium aiming to synthesize at least 100 new chemical probes and the Target 2035 initiative to accrue probes for all human targets by 2035 . As of June 2021, we were able to collect probe data from the sources listed below.