<p>Septic shock is characterized by a&#xa0;collapse of physiological circulatory regulation with profound vasoplegia, relative vasopressor insufficiency, and frequently concomitant myocardial dysfunction. In this review, we first outline the physiological roles and interactions of the three key endogenous vasopressor systems—the sympathetic nervous system/noradrenaline, arginine vasopressin, and the renin–angiotensin–aldosterone system—in maintaining blood pressure, organ perfusion, and intravascular volume. We then summarize the main mechanisms of septic vasoplegia. On this basis, we present current recommendations from the 2026 Surviving Sepsis Campaign and the 2025 update of the German S3 guideline on sepsis regarding the use of noradrenaline as a&#xa0;first-line vasopressor and vasopressin as add-on therapy, adrenaline/dobutamine in the setting of cardiac dysfunction, and corticosteroids in refractory shock. Finally, we emphasize the close interdependence of vasopressor therapy and fluid management.</p>