Epigenetic control of gene expression during cardiac development and disease has been a topic of intense research in recent years. Advances in experimental methods to study DNA accessibility, transcription factor occupancy, and chromatin conformation capture technologies have helped identify regions of chromatin structure that play a role in regulating access of transcription factors to the promoter elements of genes, thereby modulating expression. These chromatin structures facilitate enhancer contacts across large genomic distances and function to insulate genes from cis-regulatory elements that lie outside the boundaries for the gene of interest. Changes in transcription factor occupancy due to changes in chromatin accessibility have been implicated in congenital heart disease. However, the factors controlling this process and their role in changing gene expression during development or disease remain unclear. In this review, we focus on recent advances in the understanding of epigenetic factors controlling cardiac morphogenesis and their role in diseases.