The COVID-19 pandemic necessitates the development of therapeutic agents for high-risk infected patients. Sotrovimab is a monoclonal antibody with efficacy against SARS-CoV-2 and other sarbecoviruses. Its efficacy has been shown in the COMET-ICE trial, where a 500 mg infusion in non-hospitalized patients with mild to moderate COVID-19 infections and at least one risk factor for progression was associated with reduced disease progression, hospitalization and death. There was a small but statistically significant increase in self-limiting diarrhoea with sotrovimab. For hospitalized patients, there is no strong evidence of benefit with sotrovimab. The emergence of the Omicron variant was associated with reduced efficacy of sotrovimab, with subsequent increased resistance to sotrovimab by the BA.2 sub-lineage. The risk of developing resistance to monoclonal antibodies with increased use, efficacy with the emergence of variants and safety monitoring should continue to provide ongoing risk-benefit analysis of their use.