Efflux pumps are crucial in bacterial antimicrobial resistance, with clinically relevant multidrug resistance (MDR) efflux pumps encoded on the chromosome. These pumps can be specific to one substrate or transport a range of compounds, including antibiotics. They contribute to resistance in bacteria by either increasing pump expression or altering the pump protein to enhance export efficiency. Efflux pumps are found in both antibiotic-susceptible and resistant bacteria, and their role in resistance varies by species, drug, and infection. Genes for these pumps are often located on the chromosome or transmissible elements like plasmids. This review focuses on chromosome-encoded MDR efflux pumps. There are five main families of efflux pumps: RND, MFS, SMR, MATE, and ABC. The RND family, including AcrAB-TolC in E. coli and MexAB-OprM in P. aeruginosa, is particularly important. These pumps are tripartite, consisting of inner membrane, periplasmic, and outer membrane components. The MFS family includes NorA in S. aureus and PmrA in S. pneumoniae. MATE pumps, such as PmpM in P. aeruginosa, use the proton motive force or sodium gradient for transport. ABC pumps, like LmrA in Lactococcus lactis, are also involved in MDR. Efflux pumps contribute to resistance by reducing intracellular antimicrobial concentrations, allowing bacteria to survive and potentially accumulate mutations in target genes. They also play roles in natural physiological functions, such as bile tolerance and host colonization. Inhibitors of efflux pumps, including biofilms, can enhance antimicrobial activity. MDR efflux pumps are involved in the resistance of various clinically relevant bacteria, including P. aeruginosa, E. coli, S. enterica, Campylobacter spp., A. baumannii, and N. gonorrhoeae. Overexpression of these pumps can lead to resistance to multiple antibiotics, and their regulation is influenced by genetic mutations and environmental factors. The clinical relevance of efflux-mediated resistance varies, and understanding these pumps is essential for developing new antimicrobial strategies.Efflux pumps are crucial in bacterial antimicrobial resistance, with clinically relevant multidrug resistance (MDR) efflux pumps encoded on the chromosome. These pumps can be specific to one substrate or transport a range of compounds, including antibiotics. They contribute to resistance in bacteria by either increasing pump expression or altering the pump protein to enhance export efficiency. Efflux pumps are found in both antibiotic-susceptible and resistant bacteria, and their role in resistance varies by species, drug, and infection. Genes for these pumps are often located on the chromosome or transmissible elements like plasmids. This review focuses on chromosome-encoded MDR efflux pumps. There are five main families of efflux pumps: RND, MFS, SMR, MATE, and ABC. The RND family, including AcrAB-TolC in E. coli and MexAB-OprM in P. aeruginosa, is particularly important. These pumps are tripartite, consisting of inner membrane, periplasmic, and outer membrane components. The MFS family includes NorA in S. aureus and PmrA in S. pneumoniae. MATE pumps, such as PmpM in P. aeruginosa, use the proton motive force or sodium gradient for transport. ABC pumps, like LmrA in Lactococcus lactis, are also involved in MDR. Efflux pumps contribute to resistance by reducing intracellular antimicrobial concentrations, allowing bacteria to survive and potentially accumulate mutations in target genes. They also play roles in natural physiological functions, such as bile tolerance and host colonization. Inhibitors of efflux pumps, including biofilms, can enhance antimicrobial activity. MDR efflux pumps are involved in the resistance of various clinically relevant bacteria, including P. aeruginosa, E. coli, S. enterica, Campylobacter spp., A. baumannii, and N. gonorrhoeae. Overexpression of these pumps can lead to resistance to multiple antibiotics, and their regulation is influenced by genetic mutations and environmental factors. The clinical relevance of efflux-mediated resistance varies, and understanding these pumps is essential for developing new antimicrobial strategies.