Nine years ago, we published an article that suggested a specialized role for calcineurin–nuclear factor of activated T-cells (NFAT) signaling in regulating pathological cardiac hypertrophy preferentially over physiological growth and, in fact, the later response was associated with reduced calcineurin-NFAT activity. Since this time we and others have continued to uncover how this signaling effector pathway functions in the heart in regulating specific aspects of the growth response during disease and with exercise.