The mechanisms by which hypoxia increases drive to breathe remain controversial. We assessed the role in this process of the AMP-activated protein kinase (AMPK), which is central to cell autonomous adaptations during metabolic stress (Hardie, 2007). Hypoxia-evoked increases in minute ventilation were abolished by deletion of AMPK-α1 and -α2 catalytic subunits in TH(tyrosine hydroxylase)-expressing cells, which comprise a subset of those that comprise the hypoxia-responsive respiratory network, from carotid body to brainstem (Guyenet, 2000). Moreover, mice lacking AMPK exhibited marked hypoventilation and apnoea during hypoxia, rather than hyperventilation. Surprisingly AMPK deletion revealed pronounced right-left asymmetry (Vallortigara et al., 2005) with respect to the activation by hypoxia of dorsal and ventral nuclei of the caudal brainstem; assessed by functional magnetic resonance imaging. We conclude, therefore, that AMPK increases drive to breathe during hypoxia and resists apnoea via right-side dominant modulation of the respiratory network. Deficits in AMPK activity may thus compromise the capacity to accommodate respiratory depression during hypoxia, and identifies this signalling pathway as a therapeutic target for sleep disordered breathing associated with metabolic syndrome-related disorders (Chau et al., 2012; Ruderman et al., 2013).