The founding in 1965 of what is now called the Cambridge Structural Database (CSD) has reaped dividends in numerous and diverse areas of chemical research. Each of the million or so crystal structures in the database was solved for its own particular reason, but collected together, the structures can be reused to address a multitude of new problems. In this Review, which is focused mainly on the last 10 years, we chronicle the contribution of the CSD to research into molecular geometries, molecular interactions, and molecular assemblies and demonstrate its value in the design of biologically active molecules and the solid forms in which they are delivered. Its potential in other commercially relevant areas is described, including gas storage and delivery, thin films, and (opto)electronics. The CSD also aids the solution of new crystal structures. Because no scientific instrument is without shortcomings, the limitations of CSD research are assessed. We emphasize the importance of maintaining database quality: notwithstanding the arrival of big data and machine learning, it remains perilous to ignore the principle of garbage in, garbage out. Finally, we explain why the CSD must evolve with the world around it to ensure it remains fit for purpose in the years ahead.