The article reviews the role of angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of COVID-19. Both SARS-CoV and SARS-CoV-2 enter host cells via ACE2, which is expressed in various human organs. ACE2 catalyzes the conversion of angiotensin II to angiotensin-(1–7), which counteracts the negative effects of the renin-angiotensin system (RAS). The downregulation of ACE2 and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS axis may contribute to multiple organ injuries in COVID-19. The spike glycoprotein of SARS-CoV-2, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help mitigate organ injuries in COVID-19.The article reviews the role of angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of COVID-19. Both SARS-CoV and SARS-CoV-2 enter host cells via ACE2, which is expressed in various human organs. ACE2 catalyzes the conversion of angiotensin II to angiotensin-(1–7), which counteracts the negative effects of the renin-angiotensin system (RAS). The downregulation of ACE2 and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS axis may contribute to multiple organ injuries in COVID-19. The spike glycoprotein of SARS-CoV-2, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help mitigate organ injuries in COVID-19.