Introduction: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide and has contributed to over 650,000 deaths. This review synthesizes the literature on COVID-19 pharmacotherapy to inform practice and policymaking. Areas covered: The authors systematically review the published literature on COVID-19 therapeutics, grouping candidate treatments into repurposed, adjunct, and experimental agents. They conducted meta-analysis where appropriate and provide recommendations based on compilation from real-time/interim therapeutic guidelines. They then advise on how to navigate and advance the evidence in the current context of uncertainty and urgency and provide expert opinion on suggested framework. Expert opinion: Current evidence does not support a clear role for pharmacotherapy in COVID-19. While promising signals have been found through limited number of RCTs, these must be interpreted with caution. Without proper protection from bias and confounding we risk exposing patients to treatments where the potential for benefit is at best unclear, yet the potential for harm from adverse effects is high leading to a trade-off dilemma in decision making. Advancing the evidence requires a coordinated effort to design and conduct robust trials and to systematically synthesize and critically evaluate findings. Therapies should be reserved for use in clinical trials, emergency or compassionate access until we gain more confidence in the balance of benefit and harm.