Ferumoxytol is approved in the United States (U.S.) for treatment of iron deficiency anemia in chronic kidney disease. However, its superparamagnetic properties can be leveraged for off-label use in MRI. In 2015, the U.S. Food and Drug Administration (FDA) issued a “black-box” warning regarding risk of rare but serious hypersensitivity reactions based on post-marketing surveillance therapeutic use data. Preliminary experience from the FeraSafe Multi-Center RegistryTM suggests a low incidence of adverse events with the off-label diagnostic use of ferumoxytol. To date, these preliminary results suggest that with appropriate clinical use and monitoring, there is an acceptable benefit /risk profile.