To survive and perform basic metabolic processes, all living organisms must maintain a state of energy balance. Energy balance is achieved by increasing energy expenditure during periods of energy excess and decreasing energy expenditure during periods of energy deficit. In this review, we focus on 5 0 -AMP-activated protein kinase (AMPK), a heterotrimeric enzyme complex consisting of one catalytic and two regulatory subunits that is a key component in the pathway maintaining cellular and whole body energy balance. AMPK is widely expressed in mammalian as well as avian tissues. In response to states of negative energy balance, AMPK is activated through phosphorylation by upstream AMPK kinases. It then acts to increase the activities of those metabolic pathways that generate energy while decreasing the activities of energy-consuming pathways. As a result, AMPK is involved in the regulation of carbohydrate, lipid and protein metabolism. AMPK achieves its metabolic effects acutely by direct phosphorylation of many downstream target proteins and, long-term, by regulation of transcription factor and co-activator activities which leads to changes in gene transcription. AMPK responds not only to fluctuations in cellular energy level, but also to specific nutrients and hormones and thereby participates in the regulation of whole body energy balance and food intake. Recent work has begun to define the AMPK pathway in avian species where it most likely plays a similar role in maintaining energy balance and controlling food intake as it has been reported to do in mammals.