The use of nanoparticulate systems as contrast agents for magnetic resonance imaging (MRI) is well-established and known to facilitate an enhanced image sensitivity within scans of a particular pathological region of interest. Such a capability can enable both a non-invasive diagnosis and the monitoring of disease progression/response to treatment. In this review, magnetic nanoparticles that exhibit a bio-responsive MR relaxivity are discussed, with pH-, enzyme-, biomolecular-, and protein-responsive systems considered. The ability of a contrast agent to respond to a biological stimulus provides not only enriched diagnostic capabilities over corresponding non-responsive analogues, but also an improved longitudinal monitoring of specific physiological conditions.