Purpose of Review <p>Tissue perfusion is tightly regulated by central neural circuits that integrate autonomic and sensory inputs to match blood flow to tissue metabolic demand. This review synthesizes current knowledge on the central mechanisms governing tissue perfusion in both physiological and pathological states, with emphasis on the organization of brain networks involved in cardiovascular control.</p> Recent Findings <p>Recent advances reveal that tissue perfusion is modulated not only by classical reflex pathways, but also by humoral, metabolic, immune, and neuromodulatory systems. Key brain regions, particularly within the brainstem, coordinate sympathetic and parasympathetic outflows through complex and state-dependent interactions that dynamically regulate vasomotion and cardiac function. Emerging evidence also demonstrates that maladaptive remodeling of these central networks contributes to vascular dysfunction in disorders such as hypertension and heart failure, promoting tissue hypoxia and end-organ damage.&#xa0;</p> Summary <p> Central neural mechanisms play a pivotal role in the regulation of tissue perfusion under both healthy and diseased conditions. A comprehensive understanding of the neural circuits and signaling pathways involved in perfusion control may support the development of targeted therapeutic strategies aimed at restoring vascular homeostasis and improving outcomes in cardiocirculatory and neurovascular diseases.&#xa0;</p>