In most of the cases, cardiac hypertrophy is the physiological adaptation of the heart to a disease, and the causal disease is usually arterial and cardiac failure indicates the limits of the mechanical adaptation. Such an adaptational process is aggravated by an additional factor, namely fibrosis which is not related to mechanical overload, but depends upon ischemia, senescence and hormones or peptides. Myocardial adaptation or dysadaptation is a species-specific process because the regulation of calcium movements, the main myocardial intracellular messenger differs from one animal species to the other. In this chapter, we will use, as a model, the rat, and finally will report what we know concerning the biology of the human failing heart.