Epigenetic mechanisms are essential for regulating gene expression and chromatin architecture in mammalian cells, and not surprisingly they play critical roles in both normal cardiac development and heart diseases. Epigenomics refers to the study of epigenetic features at a genome-wide level. Recently, the epigenomic dynamics in heart development and cardiovascular diseases has been suggested by increasing amounts of large-scale epigenomic profiling data, including genome-wide distribution of histone modifications and DNA methylations and three-dimensional configuration of chromatin. Direct cardiac reprogramming, which serves as a promising therapeutic strategy for cardiac diseases, also involves global epigenetic changes during cell fate conversion. Thoroughly understanding epigenomic changes with computational analyses of multi-omics data will identify key epigenomic signatures in cardiac development, reprogramming, and diseases, which will provide new insights in decoding the epigenetic mechanisms in the regulation of cell plasticity and inspire novel therapeutic strategies for cardiovascular diseases.