Magnetic iron oxide nanoparticles (MIONs) are among the first generation of nanomaterials that have advanced to clinic use. A broad range of biomedical techniques has been developed by combining the versatile nanomagnetism of MIONs with various forms of applied magnetic fields. MIONs can generate imaging contrast and provide mechanical/thermal energy in vivo in response to an external magnetic field, a special feature that distinguishes MIONs from other nanomaterials. These properties offer unique opportunities for nanomaterials engineering in biomedical research and clinical interventions. The past few decades have witnessed the evolution of the applications of MIONs from conventional drug delivery and hyperthermia to the regulation of molecular and cellular processes in the body. Here we review the most recent development in this field, including clinical studies of MIONs and the emerging techniques that may contribute to future innovation in medicine.