The hypothalamus encompasses multiple neuronal circuits regulating arousal, energy homeostasis and goal-oriented behaviors. Recent observations have linked sleep perturbances with leptin and ghrelin pathways and subsequent metabolic imbalances. Thus, hypothalamic circuits sharing both sleep and metabolic functions, such as the Hypocretin (Hcrt) and Melanin-Concentrating Hormone (MCH) systems, are strong candidates for mediating these imbalances. Hcrt containing neurons receive significant input from NPY and POMC neurons in the arcuate nucleus, are regulated by leptin and hyperpolarized by glucose; hence Hcrt neurons provide a powerful sensor of metabolism that is integrated into stable wakefulness. Optogenetic manipulation of Hcrt neurons is sufficient to induce sleep-to-wake behavioral transitions. Activation of Hcrt neurons can reinstate drug and food seeking behavior in extinguished animals, demonstrating a role for this peptidergic system in motivation and goal-oriented behaviors. Here, we propose new roles for these peptidergic systems as sensors and effectors of arousal state, and discuss their implications in the plasticity of complex hypothalamic networks regulating sleep and energy balance. Finally, we suggest that new tools for remote control of neuronal circuit activity provide an effective way of testing related questions by interrogation of these circuits with unprecedented specificity and temporal resolutions.