Since its first appearance in December of 2019, regular updates around the world demonstrates that the number of new Corona Virus 2019 (COVID-19) cases are increasing rapidly, indicating that not only does COVID-19 exhibit a rapid spread pattern, but human intervention is necessary for its resolution. Up until today (27-5-2020) and according to the World Health Organization (WHO), the number of confirmed COVID-19 cases has surpassed 4.5 million with more than 307, 500 deaths. Almost all countries have been affected by COVID-19, and resultingly, various drug trials have been conducted, however, a targeted treatment remains to be made accessible to the public. Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19. We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19. Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19. ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.