During the past decade, there has been extensive investigation of bacterial resistance mechanisms. The interplay of genetic and antibiotic factors on antibiotic resistance are multiple and complex. Antibiotic resistance is the clinical expression of these factors. This article reviews the most studied and understood mechanisms of resistance in bacterial species in which resistance problems have clinical significance. Besides plasmid mediated resistance some resistance problems among respiratory pathogens are clonal resistance. The precise cause of this actual genetic event causing bacterial mutation recombination and selection is not always clear. Although resistance mechanisms may be identical within an antibiotic class, expression of resistance often varies among antibiotics of the same class.