Magnetic resonance imaging (MRI) contrast agents have been used routinely for more than 20 years in order to increase sensitivity and specificity of lesion detection. MRI contrast agents (CAs) are usually categorized according to their magnetic behavior, biodistribution, and effect on the MR image. Typically, small molecular-weight gadolinium based CAs are examples of T1 agents, while magnetic nanoparticle (MNP) based CAs are examples of T2 agents. In addition to differences in magnetic relaxation behavior, small molecular-weight gadolinium based CAs and MNP based CAs show significantly different toxicity profiles. In the case of small molecular-weight gadolinium based CAs, many previous toxicological studies have reported favorable safety profiles of gadolinium based CAs. However, recently, a delayed serious adverse reaction known as nephrogenic systemic fibrosis (NSF) has been reported in patients, with a marked reduction in renal function after administration of certain types of gadolinium based CAs. For MNP based CAs, in addition to a wide spectrum of nanotoxicity common in nanomaterials, the emerging unexpected cytotoxicity of MNPs has become a new concern. Specifically, the combination of MNPs and strong static magnetic field (SMF) within MRI may give rise to potential adverse effects of MNPs in clinical application.