Luminescent metal nanoclusters (NCs) have recently emerged as a novel class of luminescent nanomaterials and hold significant potential in biomedicine owing to their ultrasmall (< 2 nm) size, excellent photostability, and good biocompatibility. The recent rapid advances in the synthesis and functionalization of luminescent metal NCs have enabled scientists to develop colorful nanomaterials and nanodevices for a wide range of biomedical applications. In this review, we summarize the characteristics and advantages of luminescence from metal NCs, and highlight their applications in biomedicine. We focus on the research in biomedical detection, bio-imaging, drug delivery, and therapy, especially for the advances in the last five years. Luminescent metal NCs display a series of unique superiorities in biomedical applications, and the recent achievements have brought a lot of benefits to the diagnosis and treatment of clinical diseases, especially for tumors and cancers. Finally, we put forward the main challenges that currently still hinder the basic science studies and the practical development of luminescent metal NCs in biomedical applications. Overall, we expect that luminescent metal NCs will play a much more important role in future biomedicine and clinical applications.