In patients with septic shock, a mean arterial pressure higher than 65 mmHg is recommended by the Surviving Sepsis Campaign Guidelines. However, a precise mean arterial pressure target has not been delineated. The aim of this paper was to review the physiological rationale and clinical evidence for increasing mean arterial pressure in septic shock. A mean arterial pressure level lower than renal autoregulatory threshold may lead to renal dysfunction. However, adjusting macrocirculation objectives in particular after the early phase of septic shock may not correct established microcirculation impairments. Moreover, sympathetic over-stimulation due to high doses of vasopressor (needed to achieve high mean arterial pressure targets) may be associated with numerous harmful effects. Observational and small short term interventional studies did not provide a definitive answer to this question but suggested that a high mean arterial pressure (around 75-85 mmHg) may prevent acute kidney injury in some patients. The SEPSISPAM Trial, a large prospective, randomized, controlled study, compared the targets of High (i.e. 80 to 85 mm Hg) versus Low (i.e. 65 to 70 mm Hg) mean arterial pressure in patients with septic shock. The mortality was not different in the two groups. However in patients with chronic hypertension, there were significantly less renal failure in the high mean arterial pressure group than the low mean arterial pressure group.