Antibiotic resistance is a major public health threat, with multidrug-resistant organisms now found in both hospital and community settings. Bacteria adapt to antibiotics through genetic mechanisms, including mutations in genes, acquisition of foreign DNA, and changes in gene expression. Understanding these mechanisms is crucial for developing strategies to combat resistance. This review discusses the genetic and biochemical basis of antibiotic resistance, focusing on mechanisms such as target modification, reduced antibiotic penetration, and efflux pumps. Key mechanisms include enzymatic inactivation of antibiotics, production of β-lactamases, and changes in target sites. Resistance can also arise from decreased antibiotic penetration due to altered porins or efflux pumps. These mechanisms vary among bacterial species and are often facilitated by horizontal gene transfer. Examples include aminoglycoside modifying enzymes, β-lactamases, and efflux pumps. The emergence of resistance is exacerbated by the lack of new antibiotics and the spread of resistance genes through genetic exchange. Understanding these mechanisms is essential for developing effective therapeutic strategies against multidrug-resistant organisms.Antibiotic resistance is a major public health threat, with multidrug-resistant organisms now found in both hospital and community settings. Bacteria adapt to antibiotics through genetic mechanisms, including mutations in genes, acquisition of foreign DNA, and changes in gene expression. Understanding these mechanisms is crucial for developing strategies to combat resistance. This review discusses the genetic and biochemical basis of antibiotic resistance, focusing on mechanisms such as target modification, reduced antibiotic penetration, and efflux pumps. Key mechanisms include enzymatic inactivation of antibiotics, production of β-lactamases, and changes in target sites. Resistance can also arise from decreased antibiotic penetration due to altered porins or efflux pumps. These mechanisms vary among bacterial species and are often facilitated by horizontal gene transfer. Examples include aminoglycoside modifying enzymes, β-lactamases, and efflux pumps. The emergence of resistance is exacerbated by the lack of new antibiotics and the spread of resistance genes through genetic exchange. Understanding these mechanisms is essential for developing effective therapeutic strategies against multidrug-resistant organisms.