The U.S. Food and Drug Administration has issued several Emergency Use Authorizations for the use of COVID-19 therapeutics. Nirmatrelvir-ritonavir joins the list as the first oral antiviral to be administered in the outpatient setting for individuals with laboratory-confirmed COVID-19 who exhibit mild to moderate symptoms. We will review the indications, discuss currently available efficacy and safety data, and consider its place in therapy in light of the current dominant Omicron variant of concern. Product-specific requirements and counseling considerations will also be touched upon.