Energy balance and body weight are tightly regulated by homeostatic and non-homeostatic (hedonic) systems of the brain. These systems are finely tuned by hypothalamic and extrahypothalamic neurocircuitry that modulate feeding the appetite signalling cascade in response to energy of active and passive component of total daily energy expenditure (TDEE). The hypothalamic arcuate nucleus (ARC) was extensively studied and thus described as a dominant brain region involved with orchestration of all homeostatic processes, especially energy balance. However, emerging evidence indicates that the extrahypothalamic signalling has a critical role in regulation of a healthy body weight across the lifespan. Emerging evidence showed that, the brainstem nuclei of the dorsal vagal complex (DVC), including the area postrema (AP) and nucleus of the solitary tract (NTS), were shown to integrate humoral and vagal signals to modulate feeding behaviour via catecholaminergic, glutamatergic, and GABAergic activity. In essence, the DVC is deemed as a port of entry where initial appetite-related signals are first conveyed via the vagal afferents before projecting to less perfused and innervated brain regions of the forebrain. Understanding the intricate interactions and projections between hypothalamic and brainstem nuclei is essential for comprehending energy balance regulation and addressing metabolic conditions such as diabetes and obesity. Further research in this area may lead to the development of targeted interventions for managing of these metabolic disorders and promoting a healthier body weight across the life span.