Diabetes afflicts hundreds of millions worldwide. People affected by type 1 diabetes mellitus (which is the “insulin-deficient” form of diabetes) or type 2 diabetes mellitus (which is the “insulin-resistant” form of diabetes) have significantly reduced life expectancy compared to normal individuals. This is due in part to the fact that (despite improvements) current anti-diabetic approaches are suboptimal. Indeed, severe morbidities (e.g.: cardiovascular disease, hypertension) are still too often associated with diabetes. Recent preclinical results indicate that different types of hypothalamic neurons are endowed with the ability to mediate the hyperglycemia-lowering action of the adipocyte-derived hormone leptin in an insulin-dependent and insulin-independent fashion. These results may pave the way for better anti-diabetic approaches. Here, I will discuss about these hypothalamic-neuron-mediated mechanisms governing glucose metabolism in the context of “insulin-deficient” and “insulin-resistant” diabetes.