The dynamic control of energy metabolism is dependent on balancing energy demand with energy supply. In mammals this balance is maintained through the integration of many different cytokine signals that communicate the nutrient status of the organism to the hypothalamus, liver and skeletal muscle. Adipose tissue and resident macrophages secrete many of these cytokine factors including leptin, tumour necrosis factor α, adiponectin, interleukin-6 and resistin. Other secreted factors including ciliary neurotrophic factor and ghrelin have also been shown to regulate energy metabolism. The AMP-activated protein kinase (AMPK) has emerged as an important integrator of these cytokine signals regulating both central and peripheral pathways controlling food intake, energy expenditure and substrate utilization and as such is the focus of this review.