Septic shock causes unpredictable cardiovascular responses through adrenoreceptor-mediated changes in cardiac function and vascular responsiveness. The use of norepinephrine should be regarded as neurohormonal augmentation therapy to defend decompensating haemodynamic function rather than as a rescue therapy to treat shock. Recent trials represent a perceptible change in clinical practice to preferentially use norepinephrine early in resuscitation to defend the mean arterial pressure and to use norepinephrine as a neurohormone rather than as a vasopressor.