AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. This pivotal role of AMPK places it in an ideal position for regulating whole-body energy metabolism, and AMPK might play a part in protecting the body from metabolic diseases such as type 2 diabetes and obesity. Mutations in AMPK cause cardiac hypertrophy and arrhythmia. Recent findings have identified LKB1 – a protein kinase that is mutated in a hereditary form of cancer – as a candidate for the upstream kinase in the AMPK cascade. AMPK could provide a link in human diseases of which the underlying cause is due to defects in energy metabolism.