Purpose of Review Rapidly evolving treatment paradigms of coronavirus disease 2019 (COVID-19) introduce challenges for clinicians to keep up with the pace of published literature and to critically appraise the voluminous data produced. This review summarizes the clinical evidence from key studies examining the place of therapy of recommended drugs and management strategies for COVID-19. Recent Findings The global magnitude and duration of the pandemic have resulted in a flurry of interventional treatment trials evaluating both novel and repurposed drugs targeting various aspects of the viral life cycle. Additionally, clinical observations have documented various stages or phases of COVID-19 and underscored the importance of timing for the efficacy of studied therapies. Since the start of the COVID-19 pandemic, many observational, retrospective, and randomized controlled studies have been conducted to guide management of COVID-19 using drug therapies and other management strategies. Large, randomized, or adaptive platform trials have proven the most informative to guide recommended treatments to-date. Antimicrobial stewardship programs can play a pivotal role in ensuring appropriate use of COVID-19 therapies based on evolving clinical data and limiting unnecessary antibiotics given low rates of co-infection. Given the rapidly evolving medical literature and treatment paradigms, it is recommended to reference continuously updated, curated guidelines from national and international sources. While the drugs and management strategies mentioned in this review represent the current state of recommendations, many therapies are still under investigation to further define optimal COVID-19 treatment.