The disturbance of normal Ca2+ homeostasis is cardiac muscle can enhance the risk of life threatening arrhythmias. The Na+/Ca2+ exchanger (NCX) has an essential role in maintaining cardiac Ca2+ homeostasis and is considered as the main pathway for Ca2+ extrusion from the cardiomyocytes. Therefore, NCX can be assumed to play an important role in arrhythmogenesis under certain conditions such as heart failure and calcium overload. In these situations, i.e during Ca2+ overload enhanced function of NCX is associated with early (EAD) and delayed (DAD) afterdepolarizations which represent important trigger mechanisms in the generation of arrhythmias. Therefore, both selective and non-selective NCX inhibition may represent possible options for the treatment of cardiac arrhythmias. In addition, since NCX function critically depends on intra/extracellular Ca2+ concentrations and membrane potential -both dynamically changing during the action potential- NCX inhibition can also influence cardiac repolarization and dispersion of repolarization that represent substrates for arrhythmogenesis. Until very recently it was not possible to address this question directly due to the lack of specific NCX inhibitors.