Low dead cell levels detected in various cardiac pathologies led to consider cardiac apoptosis as epiphenomena without repercussion on heart function. However, apoptosis prevention, and more specifically caspase inhibition, has been associated with major myocardial contractile performance improvement. This review describes specifically caspase involvement in myocardial dysfunction and highlights typical cardiomyocyte apoptosis signaling features. Thus caspase neutralization may represent a promising therapeutic strategy in heart disease treatments.