Metal-Organic Frameworks (MOFs) have aroused great interest in the field of nanoscience and nanotechnology particularly in biomedical domains, such as Drug Delivery System (DDS), Biomedical Imaging (BI) and Photodynamic Therapy (PDT). As an emerging material, MOFs possess extraordinarily high surface area, controllable particle size and good biocompatibility. With extraordinary flexibility in the selection of organic and inorganic components, MOFs can rationally be tuned to obtain the materials having versatile structures and porosities. MOFs can serve as ideal vehicles for DDS, BI and PDT through modification and function. In this review, we summarized the design and synthetic strategies for preparing MOFs and introduced their recent advanced usage in DDS, BI and PDT. Finally, the prospect and future challenges of these nanomaterials are also documented.