The prevalence of organisms producing extended-spectrum beta-lactamases(ESBLs) has been increasing all over the world. ESBLs confer resistance to cefotaxime, ceftazidime, aztreonam, extended-spectrum penicillins, and structurally related beta-lactams in clinical isolates of K. pneumoniae and E. coli. Under the influence of antimicrobial agents, bacteria that primarily produce TEM-type or SHV-type beta-lactamases developed point mutations in structural genes which served to extend the substrate specificity of the enzymes. Infections caused by ESBLs producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat. This article provides an historical overview of the emergence of ESBLs carrying gram-negative rods and consider how to treat their infections.