Metal–organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural and compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity to retain organic (drug) molecules, metals, and gases, to effectively channel electrons and photons, to survive harsh physiological conditions such as low pH, and even to protect sensitive biomolecules. Extensive preclinical research has been carried out with MOFs to treat several pathologies and, recently, their integration with other biomedical materials such as stents and implants has demonstrated promising performance in regenerative medicine. However, there remains a significant gap between MOF preclinical research and translation into clinically and societally relevant medicinal products. Here, the intrinsic features of MOFs are outlined and their suitability to specific biomedical applications such as detoxification, drug and gas delivery, or as (combination) therapy platforms is discussed. Furthermore, relevant examples of how MOFs have been engineered and evaluated in different medical indications, including cancer, microbial, and inflammatory diseases is described. Finally, the challenges facing their translation into the clinic are critically examined, with the goal of establishing promising research directions and more realistic approaches that can bridge the translational gap of MOFs and MOF‐containing (nano)materials.