The use of manganese-based MRI contrast materials, either manganese salts or chelates, has spanned the entire timeframe of cardiac MRI. However interest in Mn compounds for cardiac MRI has been sporadic because of concerns over cardiotoxicity associated with significant concentration of free Mn2+ and notable success of gadolinium chelates in cardiac application. Initial strategies to overcome cardiotoxicity included chelation of Mn2+ to reduce the concentration of the free ion in vivo, and addition of Ca2+ in combination with Mn2+ to competitively reduce binding of Mn2+ to Ca2+ channels in the heart. Both approaches met with mixed success, but were subsequently discontinued in favor of gadolinium-based approaches. However Mn2+-based media potentially offer unique advantages for characterizing heart pathology over conventional Gd-based contrast media because Mn2+ is taken up by heart cells and retained for hours. Cellular uptake occurs through calcium channels so contrast on delayed images may be interpreted according to regional or global functional status. Since Mn2+ is retained in the heart, Mn-based media can be administered outside the magnet and the contrast pattern measured hours later to provide assessment of uptake. A key issue is whether sufficient accumulation of Mn2+ in heart cells for imaging can occur without cardiotoxicity, and findings to date indicate this is possible. This review examines the current status of Mn2+-enhanced MRI of heart with particular focus on the hypothesis that Mn2+ uptake can be interpreted in terms of heart function. Copyright © 2004 John Wiley & Sons, Ltd.