Aminoglycosides have been cinically used since 1944. Although this class of antibacterial agents has some nephrotoxicity and ototoxtcity issues, they continue to be part of the hospital armamentarium because of then rapid bactericidal activity, especially in combination with β-lactams. Bacterial resistance to aminoglycosides can be caused by modifying enzymes, changes in cell permeability, and changes in the cellular target. The clinical observation of high levels of aminoglycoside resistance most often results from the acquisition of genes that encode modifying enzymes and are often plasmid-borne. Aminoglycosides are inactivated by three classes of enzymes: