Due to the specific electron structure, distinctive optical/electronic/magnetic properties, and related high atomic number, worldwide scientists in various relevant fields have focused on the rational design of rare earth-based nano-sized contrast agents and their biomedical imaging application recently. For a long time, rare earth-doped nanoprobes have been widely used in up-conversion luminescence imaging owing to their attractive 4f electrons. Gd3+-modified nanoprobes and Gd3+-based nanomaterials with the unpaired 4f electrons have been generally used as contrast agents for T1-weighted MR imaging. In addition, rare earth-based nanosturcturs have performed well in X-ray imaging and CT imaging due to their stronger X-ray attenuation and higher atomic number than those of routinely used small iodinated molecules. This review provides a comprehensive introduction to the recent development of novel rare earth-based multi-modal nano-sized contrast agents, and their usages in the field of biomedical imaging.