As vascular tone depression is a hallmark of septic shock, administration of norepinephrine is logical in this setting. In this article, we provide and develop the following arguments for an early use of norepinephrine-the recommended first-line vasopressor-in septic shock: (I) prevention of prolonged severe hypotension, (II) increase in cardiac output through an increase in cardiac preload and/or contractility, (III) improvement of microcirculation and tissue oxygenation, (IV) prevention of fluid overload, and (V) improvement of outcome. Presence of a low diastolic arterial pressure as a marker of depressed vascular tone can be used as a trigger to initiate norepinephrine urgently.