In the adult heart, electrophysiological heterogeneity is present to guide activation and contraction. A change in electrophysiological heterogeneity, for example, during disease, can contribute to arrhythmogenesis. During development, spatial and temporal patterns of transcriptional activity regulate the localized expression of ion channels that cause electrophysiological heterogeneity throughout the heart. If we gain insight into the regulating processes that generate the electrophysiological characteristics and factors involved during development, we can use this knowledge in the search for new therapeutic targets. In this review, we discuss which factors guide the electrical patterning of atrioventricular conduction system and ventricles and how this patterning relates to arrhythmogenic disease in patients.