Antimicrobial resistance (AMR) in bacteria is a major global public health challenge that threatens the effective treatment of infectious diseases and increases morbidity, mortality, healthcare costs and treatment failure. This review examines the major mechanisms by which bacteria develop and disseminate resistance to antimicrobial agents, with emphasis on their molecular and physiological basis. Bacterial resistance may be intrinsic or acquired through spontaneous genetic mutations and horizontal gene transfer involving transformation, transduction and conjugation. The principal mechanisms discussed include enzymatic inactivation of antimicrobial agents, modification and protection of antimicrobial targets, reduced membrane permeability, active efflux, metabolic pathway modification, biofilm-associated resistance, persistence and antimicrobial tolerance. Particular attention is given to β-lactamases, including extended-spectrum β-lactamases and carbapenemases, as well as aminoglycoside-modifying enzymes, altered penicillin-binding proteins, ribosomal modification, fluoroquinolone target mutations and transferable colistin resistance. The review also highlights resistance mechanisms associated with major antibiotic classes, including β-lactams, aminoglycosides, macrolides, tetracyclines, fluoroquinolones, glycopeptides, sulfonamides, trimethoprim, polymyxins and rifampicin. The emergence of multidrug-resistant organisms results from the accumulation and interaction of multiple resistance mechanisms, thereby severely limiting therapeutic options.