The aim of the present educational review on superparamagnetic iron oxide nanoparticles (SPIONs) is to inform and guide young scientists and students about the potential use and challenges associated with SPIONs. The present review discusses the basic concepts of magnetic resonance imaging (MRI), basic construct of SPIONs, cytotoxic challenges associated with SPIONs, shape and sizes of SPIONs, site-specific accumulation of SPIONs, various methodologies applied to reduce cytotoxicity including coatings with various materials, and application of SPIONs in targeted delivery of chemotherapeutics (Doxorubicin), biotherapeutics (DNA, siRNA), and positron emission tomography (PET) imaging applications.