One cannot overstate that both vaccine and antiviral therapeutics are required to control viral infection. The caveat in the initial response to COVID-19 was that the severity of COVID-19 varied much: some patients have no symptoms, but others die on respirators. While only large randomized studies can give insight into whether the “drugs” help patients, clinicians and researchers were fooled into thinking that those who recovered early were helped by the test drug. Currently, there are only few to name in the list of efficacious therapeutics; however, we have already encountered the emergence of drug-resistant SASRS-CoV-2 variants and flaring-up upon conclusion of current chemotherapy. In my presentation, I will discuss the development of orally available therapeutics for COVID-19 employing the knowledge and skills evolved in the development of therapeutics for HIV/AIDS and hepatitis B as well as the prospect for the future.