The lack of available antiviral therapeutics against COVID-19 has accelerated the research and development of repurposed and novel therapeutics. Drugs such as remdesivir, favipiravir, dexamethasone, and others have demonstrated some clinical efficacy, although not provided a cure for COVID-19 patients. Other drugs such as hydroxychloroquine and ivermectin have not shown therapeutic superiority to placebo in clinical settings. Repurposed and experimental drugs and others have received emergency use authorization. Questions are raised on failures of developing efficient COVID-19 drugs and potential strategies to be successful. The comorbidity and personalized management of COVID-19, questions related to the management of asymptomatic SARS-CoV-2 manifestations, and home and intensive care unit treatment of COVID-19 are discussed in the chapter.