The energy sensor AMP-activated protein kinase (AMPK) is activated by metabolic stress and restores ATP levels in cells by switching off anabolic and switching on catabolic pathways. Recent discoveries demonstrate that AMPK is activated primarily by rising ADP levels and not, as previously thought, by AMP. AMPK activation is dependent on ADP-controlled phosphorylation of Thr172 on its activation loop, a mechanism of protein regulation that represents an example of an allosterically regulated modification (ARM). AMPK embodies many features of an adenylate charge regulatory system envisaged by Atkinson, where anabolic and catabolic pathway regulation is modulated by adenine nucleotide ratios. Here we discuss the current state of AMPK regulation by adenine nucleotides and we propose that AMPK functions as an adenylate charge-regulated protein kinase.