ABSTRACT Support is requested for a Keystone Symposia conference entitled Modern Phenotypic Drug Discovery: From Chemical Biology to Therapeutics, organized by Drs. Bridget Wagner, Neil Carragher, Jeremy Jenkins and Laura Kiessling. The conference will be held in Denver, Colorado from May 22-25, 2022. Phenotypic Drug Discovery (PDD) as an approach to drug discovery and chemical biology has been building momentum and excitement in both academia and industry. The convergence of new technology platforms (e.g., induced pluripotent stem cells, CRISPR-Cas9 gene editing, 3D biology, advanced imaging) with other disciplines such as cheminformatics, machine learning, and artificial intelligence have led to an exciting renaissance of PDD. This conference will bring together researchers performing or interested in phenotypic drug discovery from across academia and industry. Although modern advances in PDD span both academic and industry sectors, there are few non-commercial drug discovery-focused meetings available for the community, and the Keystone Symposia program is a premiere forum for this topic. This conference aims to share information and best practices in new PDD technologies, biological models, and human disease areas, as well as foster collaborative discussions across academia and industry. Additionally, this conference program will address several critical barriers in the field: how to improve the physiological relevance of phenotypic models and identifying a phenotypic target and understanding a compound’s mechanism of action (MoA). It is anticipated that attendees will leave with a renewed appreciation for phenotypic strategies in a wide variety of areas in chemical biology, and that the field will be advanced by expanding our collective efforts to push the boundaries of improved assay models and cutting-edge MoA technologies.