Numerous hypotheses have been considered to explain the fundamental mechanism(s) for the development of systolic dysfunction and heart failure in animals and humans with arterial hypertension. Besides contractile disturbances of cardiomyocytes and interstitial and perivascular fibrosis, cardiomyocyte loss is now being considered as one of the determinants of the maladaptive processes implicated in the transition from compensated to decompensated left ventricular hypertrophy. A number of experimental evidence suggest that exaggerated apoptosis may account for the loss of cardiomyocytes in the hypertensive left ventricle. Furthermore, some factors intrinsic and extrinsic to the cardiomyocyte emerge as potential candidates to trigger apoptosis. The elucidation of the possible interactions between these factors may be of major interest to prevent the progression to heart failure in patients with hypertensive heart disease.