Infective endocarditis (IE) is a rare disease with a potentially high mortality rate. The patient "portrait" is changing, there is an increase in the proportion of elderly people with concomitant diseases and degenerative defects, prosthetic valves and minimally invasive cardiac operations, implanted intracardiac devices, and hemodialysis. An additional significant negative contribution is made by the transformation of the etiological picture — an increase in the species diversity of pathogens, a decrease in the proportion of streptococci, a steady increase in the staphylococcal and enterococcal etiology of IE. The IE treatment success depends on the competent administration of antibacterial therapy. Clinicians are guided by two main documents: the national clinical guidelines "Infective endocarditis and infection of intracardiac devices" of 2021 and the European clinical guidelines "ESC Guidelines for the management of endocarditis" of 2023. The article summarizes updated data on the optimal prescription of antibacterial therapy, presented in a convenient and understandable format for the practicing physicians. Schemes for prescribing intravenous antibiotic therapy in a hospital are presented not only for traditional pathogens (Staphylococcus sp., Streptococcus sp. and Enterococcus sp.), but also for rare pathogens that cause significant difficulties (pathogens of the HACEK and non-HACEK group, Coxiella burnetii, Bartonella sp., Brucella sp., Tropheryma whipplei, Mycobacterium sp., fungi). Separately, the principles of empirical antibacterial therapy with the most effective treatment regimens not only for left-sided IE, but also for different variants of right-sided IE are presented in detail. New modern possibilities of outpatient oral antibiotic therapy for IE are presented. In conclusion, prospects for the development of conservative IE treatment are proposed.