Of the various cardiac arrhythmias, ventricular fibrillation (VF) is the most serious and has a primary role in mediating sudden cardiac death (SCD). Therefore, understanding the electrophysiologic processes that culminate in VF is critical for developing effective prevention and treatment of lifethreatening arrhythmias. The structural and electrophysiologic changes that predispose to SCD in chronically diseased hearts have been studied extensively, yet relatively little is known of the complex sequence of events that incite malignant arrhythmias in some patients but not in others. This represents a major obstacle in the development of clinical strategies for identifying and treating those patients at greatest risk. Consequently, SCD remains a major unresolved public health problem. Recent advances in our understanding of the molecular and biophysical bases of ventricular arrhythmias have focused attention on the possible role of cardiac repolarization in the mechanism of arrhythmias. Specifically, numerous studies have established a close association between cardiac arrhythmogenesis and heterogeneities of repolarization in the heart. Such heterogeneities are required for the development of unidirectional conduction block leading to reentrant excitation. Even in the normal heart there are considerable heterogeneities in ionic composition between cells spanning the left ventricle; yet, fortunately, SCD is rare in patients with normal hearts. Therefore, the factors responsible for transforming physiologic heterogeneities of repolarization into pathophysiologic heterogeneities undoubtedly are critical to the mechanisms underlying SCD. In this review, we present our current viewpoint on cellular repolarization alternans (which manifests clinically as microvolt T-wave alternans) as a novel mechanism for promoting pathophysiologic electrophysiologic heterogeneities that hasten electrical instability in the heart.