Electro-mechanical cardiac alternans consists in beat-to-beat changes in the strength of cardiac contraction. Despite its important role in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum calcium level (SR Ca load). However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2). In this chapter we review recent results regarding the relative role of SR Ca content fluctuations and SR refractoriness for the appearance of alternans in both ventricular and atrial cells.