By April 2021, little more than a year after its emergence, SARS-CoV-2 has infected more than 150 million people worldwide with a toll of over 3 million deaths. No antiviral treatment has shown a clear impact on survival in severe cases, and only anti-inflammatory drugs have been demonstrated with clinical efficacy. A number of vaccines are in quick clinical development, and a few are already in use under emergency-use authorization and have in general demonstrated a high level of protection, especially against severe disease. Nevertheless, control of COVID-19 worldwide is a tremendous global challenge to be faced, and SARS-CoV-2 is predicted to become endemic and subject to local epidemic dissemination in the best possible scenarios. Taking into account this scenario with rapid changes and the extraordinary effort on behalf of the scientific community and industry, at this particular moment in the development of the pandemic this chapter will review our current knowledge of Coronaviruses and their pandemic potential and will initiate what we think will be the main strategies for the development of antiviral drugs able to mitigate the most severe consequences of SARS-CoV-2 infection.