Different external stimuli trigger distinct growth programs in the cardiomyocyte. In response to hypertension or pressure overload (Pathologic), the cardiomyocyte activates a growth program characterized by the induction of a fetal gene program including increased natriuretic peptide expression and changes in sarcomere isoform gene expression. This program eventually leads to a more global pathologic remodeling including left ventricular dilation and diminished cardiac function en route to the syndrome of heart failure. In contrast, exercise (Physiologic) elicits a growth program without induction of the fetal-gene program and an increase in energy metabolic capacity that matches the increase energy demands imposed by chronic exercise. This latter program maintains normal cardiac function. MHC, myosin heavy chain; ANF, atrial natriuretic factor; BNP, brain natriuretic peptide; FAO, fatty acid oxidation; PPARα, peroxisome proliferator activated receptor α; PGC-1, PPARγ coactivator-1α.