Microglia, the resident macrophages of the brain, are highly dynamic cells continuously monitoring for alterations to their local environment. However, recent findings revealed an expanding array of functions beyond their established roles as immune sentinels and phagocytic removers of cellular debris. These include roles in synaptic organization, neuronal excitability, and trophic support for brain repair. Given the vital role of microglia in maintaining brain homeostasis, it is not surprising that several neurological diseases are associated and potentially triggered by microglial dysfunction. We recently showed that microglia in the mediobasal hypothalamus, a critical brain region involved in the regulation of metabolic homeostasis, are nutrient sensitive cells capable of instructing hypothalamic neurons in the regulation of energy homeostasis, and that microglial inflammatory signaling dictates susceptibility to diet-induced hypothalamic dysfunction and obesity. Indeed, we showed that inducing microglial activation is sufficient, on its own, to drive increased food intake and body weight gain in adult mice. More recently, we showed that microglial activation state regulates glucose homeostasis in a manner independent of its effect on body weight. These findings, taken together, logically implicate microglia in modulating the hypothalamic neurocircuitry controlling metabolic homeostasis. As such, understanding the nutritional and metabolic signals that regulate microglial responses could inform new therapeutic strategies that target microglia to prevent or treat metabolic disease.