Rare earth metal–organic frameworks (RE-MOFs) have drawn a good deal of research interest due to their unique properties (e.g., luminescence, magneticity, and intrinsic porosity). As such, RE-MOFs are regarded as promising materials in diverse biomedical applications (e.g., diagnostic and therapeutic reagents). This review is organized to highlight the current progress in the synthesis of RE-MOF nanocrystals and their eminent characteristics for enhanced clinical applicability. In particular, the potential utility of RE-MOFs has been explored with particular emphasis on drug delivery, fluorescent/magnetic resonance imaging, and biomedical sensing fields based on a comparative evaluation of the related literature. Finally, the challenges and future outlook for RE-MOFs are discussed in relation to their design strategy for the safe and efficient utilization in biomedical fields.