Metal–organic framework (MOF) materials have attracted a lot of attention for their potential biomedical applications. They offer unprecedented porosity, tunability, and versatile metal-organic chemistry that can enable novel therapeutic approaches in different indications such as cancer (immuno-)therapy, inflammation, regenerative medicine, and infectious diseases. However, this wealth of preclinical investigation has not translated effectively into the clinic. In this review, we take a translational perspective in analyzing MOF chemistry and the features of MOF (nano-)materials for different biomedical applications. We also assess the remaining barriers to clinical translation of MOFs and critically discuss possible approaches towards realistically bridging the translational gap and, ultimately, generating clinical impact.