Mechanical dysfunction remains as one of the best predictors of sudden cardiac death (SCD), but despite this close association the causal relationships between electrical instability and mechanical dysfunction are not fully understood. (Bigger et al., 1984;Buxton et al., 1984) Even though the effects of electrical instability on mechanical dysfunction of the heart is well appreciated and relatively clear, the reverse effects that mechanical dysfunction have electrical instability, or mechano-electrical feedback (MEF), are not. (Kohl et al., 2006;Lab, 1996) Stretch activated channels, for example, are one way mechanical activity can directly influence electrical activity at the cellular level under physiologic and pathophysiological conditions. (Hu et al., 1997) Alternatively, intracellular calcium, which regulates mechanical contraction, can significantly influence electrical function of the heart as well. The mechanisms by which intracellular calcium governs electrical instability of the heart is the main focus of this manuscript. Traditionally, calcium mediated arrhythmogenesis is associated with delayed after depolarizations and abnormal impulse formation. (Katra et al., 2007;Liu et al., 2006;Rosen, 1985;Ter Keurs et al., 2006;Wehrens et al., 2003) However, in this manuscript we focus on how cardiac alternans, a mechanisms of reentrant excitation, is another significant way mechanical dysfunction and arrhythmogenesis are causally related.Cardiac alternans can refer to either mechanical (contractile) or electrical (repolarization) oscillations that occur on an every other beat basis. Cardiac alternans has been recognized for more than 100 years. Shown in Figure 1 (Panel A) is a very early record of arterial pressure measured during a steady state heart rate, where pulse magnitude alternates on every other beat (arrows). (Traube, 1872) At this time, the ECG had not been invented; however, soon after its introduction electrical alternans was reported as well. Shown in Panel B (Figure 1) is an early example of electrical alternans as evidenced by oscillations of the ECG T-wave (arrows) and QRS. (Lewis, 1910) Soon after cardiac alternans was first reported, it was associated with a poor prognosis. (Windle, 1913) Surprisingly, at this same time several important characteristics of cardiac alternans were observed, such as alternans occurring in a structurally normal heart and appearing at faster heart rates. Subsequently, Twave alternans was more directly related to coronary artery occlusion and shown to be highly reproducible. (Hellerstein et al., 1950)