Heart failure is a progressive muscular disorder leading to a deterioration of the heart characterized by a contractile dysfunction and a chronic energy deficit. As a consequence, the failing heart is unable to meet the normal metabolic and energy needs of the body. The transition between compensated left ventricular hypertrophy and the de-compensated heart is multifactorial, although metabolic disturbances are considered to play a significant role. In this respect, the AMP-activated protein kinase (AMPK) could be a potential target in heart failure development. AMPK senses the energy state of the cell and orchestrates a global metabolic response to energy deprivation. We briefly review here the current knowledge about the chronic energy deficit of the failing heart, as well as the role of AMPK in energy homeostasis and in the control of non-metabolic targets in relation to cardiac hypertrophy and heart failure. The relative importance of energetic and non-metabolic effects in the potential cardioprotective action of AMPK is discussed.