The article provides an overview of the mechanisms by which bacteria develop resistance to antimicrobial agents. Initially, it highlights the significant impact of antimicrobial resistance on global morbidity and mortality, particularly in the context of infectious diseases. The introduction discusses the historical perspective, noting that while antibiotics were once seen as a panacea, they have since been outpaced by the ability of microorganisms to evolve resistance. The main mechanisms of resistance are categorized into four groups: limiting drug uptake, modifying drug targets, inactivating drugs, and active drug efflux. These mechanisms can be either innate or acquired through horizontal gene transfer. The article also distinguishes between resistance and persistence, explaining that persistence refers to non-susceptible cells that are not resistant due to the stationary phase of growth. The origins of resistance are explored, including natural resistance and acquired resistance through genetic material transfer. The mechanisms of resistance are detailed, with specific examples provided for each category. The article concludes by emphasizing the need for continued research and innovation in antimicrobial therapy to combat the growing threat of antimicrobial resistance.The article provides an overview of the mechanisms by which bacteria develop resistance to antimicrobial agents. Initially, it highlights the significant impact of antimicrobial resistance on global morbidity and mortality, particularly in the context of infectious diseases. The introduction discusses the historical perspective, noting that while antibiotics were once seen as a panacea, they have since been outpaced by the ability of microorganisms to evolve resistance. The main mechanisms of resistance are categorized into four groups: limiting drug uptake, modifying drug targets, inactivating drugs, and active drug efflux. These mechanisms can be either innate or acquired through horizontal gene transfer. The article also distinguishes between resistance and persistence, explaining that persistence refers to non-susceptible cells that are not resistant due to the stationary phase of growth. The origins of resistance are explored, including natural resistance and acquired resistance through genetic material transfer. The mechanisms of resistance are detailed, with specific examples provided for each category. The article concludes by emphasizing the need for continued research and innovation in antimicrobial therapy to combat the growing threat of antimicrobial resistance.