Nature Reviews Drug Discovery, Published online: 24 August 2026; doi:10.1038/s41573-026-01509-0 Drug discovery for psychiatric disorders is a slow and challenging process, driven in part by reliance on symptom-based diagnostic criteria that fail to capture the underlying disease biology. In their Perspective, Etkin and co-authors suggest a framework for a precision psychiatry approach, drawing on examples from oncology and neurology and providing initial examples for proof of principle. They discuss important biomarkers that could be used to define patient subpopulations for clinical trials and provide mechanism-based readouts to expedite psychiatric drug development.