The manganese ion (Mn2+ ) has long been used in biomedical research as an indicator of calcium (Ca2+ ) influx in conjunction with fluorescent microscopy because it is well established that Mn2+ enters cells through voltage-gated Ca2+ channels. Mn2+ is also paramagnetic, resulting in a shortening of the spin-lattice relaxation time constant, T1 , which yields positive contrast enhancement in T1 -weighted magnetic resonance imaging (MRI), specific to tissues in which the ion has accumulated. Manganese-enhanced MRI (MEMRI) uses a combination of these properties of Mn2+ to elucidate anatomical information and to identify regions of cellular activity. The focus of this chapter will detail some of the current MEMRI methodologies and biological applications.