White adipose tissue (WAT) plays an important role in the integration of whole-body metabolism by storing fat and mobilizing triacylglycerol when needed. The released free fatty acids can then be oxidized by other tissues to provide ATP. AMP-activated protein kinase (AMPK) is a key regulator of metabolic pathways, and can be targeted by a new generation of direct, small-molecule activators. AMPK activation in WAT inhibits insulin-stimulated lipogenesis and in some situations also inhibits insulin-stimulated glucose uptake, but AMPK-induced inhibition of β-adrenergic agonist-stimulated lipolysis might need to be re-evaluated in vivo. The lack of dramatic effects of AMPK activation on basal metabolism in WAT could be advantageous when treating type 2 diabetes with pharmacological pan-AMPK activators.