Fragment-based drug discovery (FBDD) has led to dozens of clinical compounds, including eight approved drugs. For the past decade, we have published an annual review of successful fragment-to-lead (F2L) medicinal chemistry programs. This Perspective marks the tenth in the series. We analyze the 18 F2L case studies from 2024 and put them in the context of the larger set of 233 examples dating back to 2015. We hope that the lessons herein will both inform and inspire researchers to discover the next generation of drugs.