In the search for novel antiarrhythmic strategies, the cardiac Na+/Ca2+ exchanger (NCX) seems to be a promising
target. Recent insights into the role of NCX in proarrhythmia stem from transgenic murine models with knockout or
overexpression of NCX. There are significant differences regarding cellular electrophysiology, excitation-contraction
coupling and Ca2+ handling when comparing mice to higher mammal and most importantly human physiology. We here
review findings derived from transgenic mouse models regarding the role of NCX in the generation of arrhythmia and discuss
principle aspects to consider when translating physiological and pathophysiological mechanisms from mouse models
into human physiology and the clinical context.