Iron overload can lead to iron deposits in many tissues, especially in the heart. It has also been shown to associate with elevated oxidative stress in tissues. Elevated cardiac iron deposits can lead to iron overload cardiomyopathy, a condition which provokes mortality due to heart failure in iron-overloaded patients. Currently, the mechanism of iron uptake into cardiomyocytes is still not clearly understood. While divalent metal transporters (DMT1) and transferrin-bound transporters play an important role in cellular iron uptake under normal physiological conditions, L-type Ca2+ channels (LTCC) have been demonstrated to be an important pathway for ferrous iron (Fe2+) uptake into cardiomyocytes under iron overload conditions. Despite growing evidence that supports the role of LTCC on iron uptake into cardiomyocytes, controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC's role as a portal for iron uptake in cardiac cells. Recently, a novel Zinc transporter 14 (Zip14) has been shown to play an important role for iron uptake into hepatocytes. Since its expression in the liver is similar to that in the heart, it is possible that Zip14 could be another portal for iron uptake into cardiomyocytes. In this review, comprehensive findings collected from previous studies as well as discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to better treatment and prevention strategies, particularly in iron-overloaded patients. © 2009 Elsevier Ireland Ltd. All rights reserved.