Angiotensin II (ANGII) is a vasoconstrictive eighth amino acid peptide, which increases blood pressure within a complex regulatory and counterregulatory system (Fig. 1). ANGII is the key molecule in the renin–angiotensin–aldosterone system (RAAS), which, together with catecholamines and vasopressin, maintains blood pressure and fluid homeostasis. These properties make angiotensin II a potential vasopressor drug for vasodilatory hypotension and/or shock in the intensive care unit (ICU). However, ANGII has not been commercially available until recently despite the fact that it had already been used safely in human studies for a long time [1]. In 2009, experimental work in Gram-negative septic sheep introduced the concept that septic acute kidney injury (AKI) may be partly due to efferent arteriolar vasodilatation and reported a marked beneficial effect of ANGII infusion on renal function [2]. This “rediscovery” of ANGII led to pilot work in humans [3] and then to the commercial development of an ANGII preparation (Giapreza^®, La Jolla, San Diego, CA). This was followed by the Angiotensin II for the Treatment of High-Output Shock III (ATHOS-3) trial [4, 5]. This international multicentre double-blind, randomized controlled trial (DB RCT) aimed to obtain Federal Drug Administration (FDA) (with a cautionary note that it might increase the risk of thrombotic events) approval by demonstrating that, in catecholamine-refractory vasodilatory shock receiving > 0.2 µg/kg/min of norepinephrine equivalent, the administration of ANGII would increase mean arterial pressure (MAP) at 3 h of infusion by either 10 mmHg or to ≥ 75 mmHg without any increase in background vasopressors. ATHOS-3 compared 163 ANGII-treated patients to 158 placebo-treated patients. Most had septic shock. The trial demonstrated an eightfold greater odds ratio of achieving MAP target with ANGII, with success in 70% vs 23% of cases with placebo. The drug is now FDA-approved as a second-line vasopressor for the treatment of catecholamine-refractory vasodilatory shock. In the United States of America (USA), it has been used in thousands of patients. It is now also approved by the European Medicines Agency (EMA) for the same indication. In late 2020, it was used to support the circulation among hypotensive patients affected by coronavirus disease 2019 (COVID-19) [6] and has now also been used in cardiac surgery patients [7]. ANGII is now commercially available in Europe.