The scientific and organizational landscape that underpins drug discovery is in a state of rapid evolution. The cellular signal transduction processes and biochemical pathways that enable life are increasingly understood at the molecular level and hypotheses for disease intervention can be proposed within this rational context. Technology to enable discovery of ligands to perturb the function of biological targets continues to advance and new methods to create small molecule tools to interrogate biological processes and potentially serve as drug leads are under development. However, while industry investment in R&D has grown exponentially, approval of new medicines has remained constant for several decades. Juxtaposition of this scientific opportunity, the continuing societal need for new drugs, and a failing model for translation of basic research into new medicines provides fertile soil for new ideas and approaches. This meeting will focus on addressing these challenges in drug discovery with an emphasis on novel biological targets, new chemical space and emerging organizational approaches to more effective translation. The goals of the meeting are: • To explore relatively uncharted protein target class families to define new druggable biological space • To survey promising new chemical approaches for ligand discovery • To highlight new organizational constructs for drug discovery with an emphasis on public/private partnerships The meeting aims to bring together medicinal chemists, disease biologists, chemical biologists, assay developers, and screeners from industry and academics, along with leaders of R&D organizations to create a dynamic exchange around the challenges facing drug discovery.