The renin-angiotensin-aldosterone system (RAAS) is a complex network of vasoactive peptides that regulate key physiological processes. SARS-CoV-2, the virus causing COVID-19, interacts with the RAAS through angiotensin-converting enzyme 2 (ACE2), which also serves as a receptor for the virus. There are concerns that RAAS inhibitors, such as ACE inhibitors and ARBs, may affect ACE2 levels and activity, potentially influencing viral infection severity. However, current human data are insufficient to support or refute these hypotheses. Studies show that ACE2 is widely expressed in various tissues, including the lungs, and plays a role in counteracting RAAS activation. While some animal studies suggest that RAAS inhibitors may increase ACE2 expression, human studies have shown mixed results. Plasma ACE2 levels may not accurately reflect the activity of the full-length membrane-bound form. The effects of RAAS inhibitors on ACE2 expression and activity in humans remain uncertain. Despite these uncertainties, there is concern that discontinuing RAAS inhibitors in high-risk patients with COVID-19 could be harmful. RAAS inhibitors have established benefits in protecting the heart and kidneys, and their withdrawal may lead to clinical decompensation in patients with cardiovascular disease. Clinical trials are ongoing to evaluate the safety and efficacy of RAAS modulators, including recombinant ACE2 and ARBs like losartan, in treating COVID-19. In patients with stable conditions, RAAS inhibitors should generally be continued, as the potential risks of discontinuation outweigh the theoretical concerns about their effect on ACE2 and viral infection. Abrupt withdrawal may lead to adverse health outcomes, particularly in patients with heart failure or a history of myocardial infarction. Careful monitoring is needed when switching from a RAAS inhibitor to another antihypertensive therapy to avoid rebound increases in blood pressure. Individualized treatment decisions are recommended for patients with chronic kidney disease. Until more data are available, RAAS inhibitors should be continued in patients at risk for, being evaluated for, or having COVID-19.The renin-angiotensin-aldosterone system (RAAS) is a complex network of vasoactive peptides that regulate key physiological processes. SARS-CoV-2, the virus causing COVID-19, interacts with the RAAS through angiotensin-converting enzyme 2 (ACE2), which also serves as a receptor for the virus. There are concerns that RAAS inhibitors, such as ACE inhibitors and ARBs, may affect ACE2 levels and activity, potentially influencing viral infection severity. However, current human data are insufficient to support or refute these hypotheses. Studies show that ACE2 is widely expressed in various tissues, including the lungs, and plays a role in counteracting RAAS activation. While some animal studies suggest that RAAS inhibitors may increase ACE2 expression, human studies have shown mixed results. Plasma ACE2 levels may not accurately reflect the activity of the full-length membrane-bound form. The effects of RAAS inhibitors on ACE2 expression and activity in humans remain uncertain. Despite these uncertainties, there is concern that discontinuing RAAS inhibitors in high-risk patients with COVID-19 could be harmful. RAAS inhibitors have established benefits in protecting the heart and kidneys, and their withdrawal may lead to clinical decompensation in patients with cardiovascular disease. Clinical trials are ongoing to evaluate the safety and efficacy of RAAS modulators, including recombinant ACE2 and ARBs like losartan, in treating COVID-19. In patients with stable conditions, RAAS inhibitors should generally be continued, as the potential risks of discontinuation outweigh the theoretical concerns about their effect on ACE2 and viral infection. Abrupt withdrawal may lead to adverse health outcomes, particularly in patients with heart failure or a history of myocardial infarction. Careful monitoring is needed when switching from a RAAS inhibitor to another antihypertensive therapy to avoid rebound increases in blood pressure. Individualized treatment decisions are recommended for patients with chronic kidney disease. Until more data are available, RAAS inhibitors should be continued in patients at risk for, being evaluated for, or having COVID-19.