Heart valves are critically important to ensure one way blood flow through the embryonic heart, which is essential for nutrient distribution and gestational progression. In just a few weeks in the human, the heart morphs from a single pulsatile tube to a four chambered pumping organ complete with valves and conduction system; with 100 fold increases in volume. Simultaneously within this cyclic and demanding hemodynamic environment, the valve primordia remodel from wispy globular masses dubbed ‘cushions’ to thin fibrous leaflets. Our lab has focused on understanding the role of mechanical signaling in controlling embryonic myocardium and valvular tissue maturation. We apply a combination of in vitro experimentation, computational simulations, and experimental and genetic animal model research tools, many of which developed in our lab. We are beginning to uncover a complex mechano-genetic signaling sequence that guides embryonic valve progenitors towards quiescent fibroblast phenotypes and their creation of striated collagenous matrix. I will also give examples of how this program is reactivated pathologically in postnatal conditions, and how developmental biology can be used to improve regenerative medicine strategies for heart valves.