In the recent years Magnetic Resonance Imaging has evolved into one of the most powerful diagnostic techniques in medicine, in part thanks to the application of suitable contrast agents. The design of new, more efficient MRI contrast media requires the complete understanding of all factors and mechanisms that influence proton relaxivity, hence efficiency of Gd(III) complexes. In this chapter we give an overview of our current knowledge in this field by shortly surveying theory and citing the most illustrative examples. We discuss each of the underlying factors, including the possible ways of their determination. Most recent developments in the field of electron spin relaxation and outer sphere relaxivity have also been reviewed. The last part is devoted to the comparison of the isoelectronic Eu(II) and Gd(III) complexes, which can give insight into the relaxation mechanisms of paramagnetic lanthanides in general, and thus help design novel Gd(III) based agents.