The presented article discusses the issue of overcoming antibiotic resistance in modern conditions. The main focus is on the formation of biofilms by microorganisms as one of the key mechanisms of antibacterial resistance. One of the key problems with the use of antibiotics for the treatment of biofilms is the necessity to achieve the required minimum inhibitory concentration (MIC) of the drug at the biofilm site, which may be 100-800 times greater than the MIC for planktonic cells. Considering the significant human and financial costs, there is an increasing need to develop new strategies for therapeutic intervention in biofilms. The effectiveness of treatment is linked to the ability of the antimicrobial agent to penetrate the heterogeneous structure of the bacterial colony's substrate. It has been shown that the ability of the drug to penetrate the biofilm depends on the structure of the matrix, the genus and strain of the bacteria, as well as the selected antibiotic. Strategies for the penetration of major antibacterial drugs into the biofilm matrix are provided, in particular the use of combination drugs such as thiamphenicol glycinate acetylcysteinate (TGA). The possibilities of using TGA in various conditions — chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, and rhinosinusitis — are discussed. In addition, data are presented on the positive impact of N-acetylcysteine (NAC) on biofilms in various other locations, including gastroenterology and catheter-associated infections. A review of the available medical literature shows that NAC in combination with thiamphenicol possesses, in addition to antibacterial properties, the ability to influence biofilm formation and disrupt biofilm function. The use of NAC may be a new strategy for the treatment of chronic respiratory infections associated with colony-forming microorganisms.