Genetic programming determines differentiation of cardiomyocytes from mesodermal precursor cells, the proper structure of developing embryonic hearts, and adapative or maladaptive responses to cardiac injury/stress. Conventional genetic regulatory mechanisms for these processes have been defined, revealing central roles for a handful of cardiac transcription factors. Similarities in regulated gene expression observed in embryonic versus injured or diseased adult hearts became the conceptual foundation for the notion that recapitulated embryonic gene expression is a marker (and potential mediator) of heart disease in adults, the so-called “fetal gene program”. Recent technological advances in genomics have revealed, in addition to the established transcriptional pathways, multiple epigenetic mechanisms that contribute to the overall transcriptional landscape of developing and diseased hearts. We will review the mechanism by which non-coding RNAs, derived from what has in the past been considered “junk DNA”, post-transcriptionally (microRNAs) and epigenetically (long non-coding [lnc] RNAs) orchestrate gene and gene product expression. We will evaluate accumulating evidence that DNA methylation, chromatin remodeling, and histone modification are dynamic processes that modulate gene expression in cardiac development and disease. Finally, we will consider an integrated model in which these epigenetic mechanisms mutually interact to govern and direct transcription factor-mediated cardiac gene expression.