CNS disorders represent a major unmet medical need. The associated societal burden is becoming unsustainable due to changing demographics (e.g., aging population). Despite major investments in basic and translational research by government and non-profit institutions world-wide, pharmaceutical companies and equity investors continue to view brain therapeutics as a relatively risky area of investment. This Keystone Symposia conference will highlight groundbreaking technologies and new approaches to de-risk CNS-targeted therapies and demonstrate how interdisciplinary integration has the potential to overcome the contemporary challenges of CNS drug development. One of the unique features of this conference is that it brings together a diversity of scientists, who rarely participate in the same meetings, in order to create an environment for disruptive innovation. Invited speakers will provide both general and technical presentations to engage participants in topics like disease biology-informed target selection, novel medicinal chemistry approaches, biomarkers, and clinical trial design. Advances in technologies such as genomics, imaging and brain delivery will be highlighted throughout. Our featured speakers hail from around the world and represent both public and private sector and young and established scientists. The aim of this conference is to create a space for collaboration that helps attendees address the unmet medical need of CNS disorders even after it has ended. Finally, this meeting will be paired with the Keystone Symposia conference on Cerebral Fluid Flow and Function: Lymphatics, Glymphatics and the Choroid Plexus. The goal of this paring is to stimulate cross-disciplinary thinking about CSF-based medicinal therapies.