Antimicrobial‍‌‍‍‌‍‌‍‍‌ resistance (AMR) has become one of the major issues affecting worldwide health. Data from the latest surveillance reports indicate that the proportion of bacterial infections that are resistant to the first-line drugs is increasing, and if no actions are taken the mortality figures will escalate exponentially. The scientific response to this problem involves two parts: Firstly - only minor but still significant improvements in the standard antibiotic pipeline, and secondly - a fast growth of nonregular antimicrobial methods and support technologies. Several new antibacterial agents and combination therapies have been approved and advanced by regulatory agencies and the industry in the last few years. Besides, clinical pipelines now have the candidates with new targets or potentiator strategies which are aimed at overcoming the resistance mechanisms. However, it is emphasized that there are very few completely new chemical classes that pose a big challenge to the discovery of antibiotics that are both safe and broadly effective. Simultaneously with the work on small molecules, alternative modalities have been shifted from the experimental stage to clinical evaluation. Bacteriophage therapy, phage-derived lysins, antimicrobial peptides, CRISPR-based antimicrobials, and microbiome-modulating strategies have gained a lot of traction in the preclinical studies, and also the evidence at the case and trial levels is increasing, particularly for the treatment of drug-resistant infections, which are either highly refractory or device-associated and involve biofilms. These strategies provide high target specificity and new modes of action that can be used to supplement antibiotics - or in certain cases to replace them - as traditional ones.