A finite number of transcription factors constitute a combinatorial code that orchestrates cardiac development and the specification and differentiation of myocytes. Many, if not all of these same transcription factors are re-employed in the adult heart in response to disease stimuli that promote hypertrophic enlargement and/or dilated cardiomyopathy, as part of the so-called “fetal gene program”. This review will discuss the transcription factors that regulate the hypertrophic growth response of the adult heart, with a special emphasis on those regulators that participate in cardiac development.