The field of molecular imaging has been defined as the noninvasive, quantitative, and repetitive imaging of biomolecules and biological processes in living organisms. Magnetic resonance (MR) is a particularly attractive platform for molecular imaging due to the ability of MR instruments to acquire high-resolution anatomical images, merely by relying on inherent differences between tissues and tissue states. Contrast agents are seen as essential to the task of molecular imaging to increase both the sensitivity and specificity of imaging. Superparamagnetic iron-oxide (SPIO) nanoparticles are spin-spin relaxation (T2) enhancers. Typically they are comprised of an iron-oxide core enveloped in a polysaccharide or synthetic polymer coating. SPIOs are expedient contrast agents thanks to their ease of synthesis, low cost, capacity for derivatization to targeting molecules, and small size. A plethora of molecular imaging applications, both in vivo and in vitro, has been developed to facilitate the use of SPIO for the purposes of diagnostics. Iron is an essential element for human beings and is critical for the delivery of oxygen and the proliferation/survival of all cells; SPIO can enter the body's normal iron metabolism cycle following uptake by the reticuloendothelial system. Passive targeting relies on exploitation of natural pharmacokinetic and phagocytic mechanisms to localize and accumulate SPIO particulates. Active targeting provides a means to image the presence and localization of an immense library of biomedically relevant molecules.