Note: Funding Information: The authors are investigators in the Randomized, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) angiotensin-converting enzyme 2 (ACE2) renin-angiotensin system (RAS) Domain (Drs. Lawler, Derde, McVerry, van de Veerdonk) and the angiotensin II receptor blockers (ARBs) CORONA II (Host Response Mediators in Coronavirus [COVID-19] Infection - Is There a Protective Effect of Losartan on Outcomes of Coronavirus Infection?) (Dr. Russell) trials—both trials that are evaluating the efficacy of RAS modulating strategies in patients hospitalized with COVID-19. ACE inhibitors and ARBs are not approved for use in the treatment of acute lung injury—all discussion above is investigational. Dr. Lawler received funding from a National New Investigator Award from the Heart and Stroke Foundation of Canada, the Canadian Institutes for Health Research (CIHR), the U.S. National Institutes of Health (NIH), the Peter Munk Cardiac Centre, the LifeArc Foundation, the Thistledown Foundation, the Ted Rogers Centre for Heart Research, and the Government of Ontario; has served as a consultant for Novartis, CorEvitas, and Brigham and Women’s Hospital; and received royalties from McGraw-Hill Publishing. This article discusses the off-label product use of ACE inhibitors and ARBs. Dr. Derde’s institution received funding from the European Union (EU) (FP7-HEALTH-2013-INNOVATION-1, grant number 602525), the EU (H2020 Rapid European COVid-19 Emergency Response grant agreement no 101003589), ZonMw (ANAkinra voor de behandeling van CORonavirus infectious disease 2019 op de Intensive Care; project number 10150062010003); she disclosed that Roche Products, Sanofi, Aventis Parma, Swedish Orphan Biovitrum AB (Sobi, Stockholm, Sweden), and Faron Pharmaceuticals all provided drugs for REMAP-CAP; she received funding from Interactie opleidingen and travel reimbursement for international conferences (European Society of Intensive Care Medicine, International Symposium on Intensive Care and Emergency Medicine, Weimar Sepsis Update, National Danish ICU Society, National Dutch ICU Society, European Respiratory Society, Critical Care Reviews). Dr. McVerry’s institution received funding from the NIH and Bayer Pharmaceuticals; he received funding from Boehringer Ingelheim, the NIH, Bayer Pharmaceuticals, the Pittsburgh Foundation, and the Translational Breast Cancer Research Consortium. Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to: 1) the use of proprotein convertase subtilisin/kexin type 9 inhibitor(s) in sepsis, 2) the use of vasopressin in septic shock, and 3) a patent owned by Ferring for use of selepressin in septic shock; he is an inventor on these patents; he was a founder, Director, and shareholder in Cyon Therapeutics and is a shareholder in Molecular You Corp; he is no longer actively consulting for any industry; he reports receiving consulting fees in the last 3 years from: SIB Therapeutics LLC (developing a sepsis drug); Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin); he was a funded member of the Data and Safety Monitoring Board of an NIH-sponsored trial of plasma in COVID-19 (Passive Immunity Trial for Our Nation [PASS-IT-ON]) (2020–2021); PAR Pharma (sells prepared bags of vasopressin); he reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC; he has received four grants for COVID-19 research from the CIHR and three grants from the St. Paul’s Foundation; and he was a nonfunded Science Advisor and member, Government of Canada COVID-19 Therapeutics Task Force (June 2020 to June 2021). Dr. van de Veerdonk’s institution received funding from Gilead and Sobi.