The worrying increase in the spread of multidrug resistant bacteria combined with the lack of new and effective antibiotics, poses a threat to global health. The factors that contribute most to the emergence of antimicrobial resistance are: limited availability of diagnostic methods, misuse and overuse of antibiotics, overuse of antibiotics in agriculture, mismatch between the discovery of new antibiotics and the speed of emergence and spread of antibiotic resistance, lack of antibiotic control programs and poor infection prevention and control. The main antibiotic groups used to treat resistant Gram-negative infections are carbapenems, fluoroquinolones, aminoglycosides and polymyxins. The mechanisms of antimicrobial resistance fall into four main categories: enzymatic degradation of antibacterial agents, alteration of a drug target, limiting uptake of a drug and active drug efflux. Some of the most important Gram-negative pathogens causing serious infections due to increasing multidrug resistance are Enterobacterales, Acinetobacter spp. and Pseudomonas spp. The worrying prevalence of carbapenemase-producing bacterial strains is increasingly reducing the efficacy of broad-spectrum carbapenems. The development of new antibiotics is a long-term process, and new antibiotics rarely appear. One of the most important steps in the fight against resistance is the use of faster and cheaper diagnostics that would allow directed antibiotic therapy and reduce the excessive and inappropriate use of antibiotics. Education of the healthcare workers and control over the prescription of antibiotics can help control the growing problem of resistance.