Staphylococcal infections are widespread among outpatients and hospitalized patients. Despite the apparent diversity of the “menu” of anti-staphylococcal drugs, treatment results in several patients are not good as expected. This is due to the properties of pathogens exhibiting various mechanisms of antimicrobial resistance, including biofilm formation, limited penetration of the drug into the focus of infection, which is largely dependent on its location, as well as basic characteristics of antimicrobial agent (activity, ability to achieve bactericidal concentrations in infectious foci, and toxicity). This review provides up-to-date information on the ways to improve treatment of patients with infections caused by Staphylococcus aureus.