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Innovation and productivity in pharmaceutical drug discovery have been below expectations. Surprisingly, more first-in-class small molecule drugs approved by the FDA (1999-2008) were identified by functional approaches reminiscent of pre-genomics pharmacology (phenotypic drug discovery) than by contemporary molecular targeted strategies. This observation, and the unexpected difficulties of target validation, have diminished the impact of the “genomics revolution” and are arguably associated with the decline in innovation and productivity of pharmaceutical research. As a result, pharmaceutical researchers have begun to reevaluate the “Molecular Mindset” which has dominated our collective drug-hunting culture, and explore modern approaches to phenotypic screening. However, there is currently no single scientific forum where scientists from pharma, biotech, academia and instrument/service providers can meet and discuss strategies/issues related to phenotypic drug discovery (PDD). In part, this is because PDD encompasses multiple therapeutic areas and involves diverse disciplines including drug discovery, chemistry, cell biology, stem cell biology, systems biology, genomics, bioengineering and informatics. This Keystone Symposia meeting uniquely provides this interdisciplinary environment and is a particularly attractive venue given the increasing role of academia in drug discovery research. The conference will be a forum for the global PDD research community in which scientists from diverse institutions and scientific disciplines can meet to share/discuss/debate topics related to advantages/disadvantages of PDD and how PDD can complement targeted approaches. Significantly, the conference will provide a much needed forum for the growing interest in PDD, and can conceivably become the cornerstone of the global scientific movement for the reintroduction of functional biology/physiology-driven pharmaceutical research.