The COVID-19 pandemic was accompanied at different times by the prescription of various drugs. The prescription of antibacterial drugs was regarded differently, and even the term “pneumonia” was the subject of discussion. The frequency of antibiotic use during the pandemic varied widely across countries, with a general trend towards overprescribing. According to most studies, in the early period of this viral infection, there were no indications for antibiotic therapy, while later, when a bacterial process is attached, a rational choice of the drug is important, taking into account the potential resistance of the pathogen, including the production of beta-lactamase. In the current version of the guidelines on COVID-19, the topic of bacterial infections has been carefully worked out. It is clearly stated that antibiotic therapy is prescribed only if there are convincing signs of a bacterial infection. On the one hand, it was noted that most patients with COVID-19 do not need antibiotic therapy, and on the other hand, for patients who do not need hospitalization with signs of a bacterial infection, amoxicillin and amoxicillin/clavulanate are the drugs of choice. The latter combination is also approved for hospitalized patients. Literature analysis has shown that amoxicillin/clavulanate remains a highly effective antibiotic for the initial treatment of community-acquired respiratory tract infections. In the conditions of import substitution, the creation of effective and safe, affordable domestic generics that have therapeutic equivalence with original drugs is a significant achievement of the Russian pharmaceutical science and industry. This review assesses the efficacy and safety of antibiotic use during a pandemic, as well as the place of amoxicillin/clavulanate in modern clinical practice.