Mn(II) has several favorable physicochemical characteristics and a good toxicity profile, which makes it a viable alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Although many studies have been undertaken in the last 10 years, this is a field of investigation still in rapid and continuous development. This review aims to critically discuss the chemical and magnetic properties of Mn(II) compounds relevant as MRI probes, both small complexes and nanosystems containing a large number of metal centers, the possible approaches for optimizing their efficiency by understanding the role of various molecular parameters that control the relaxation processes, and the most important issues related to stability and kinetic inertness.