Extended-spectrum beta-lactamases (ESBLs), which confer resistance to third generation cephalosporins, demonstrate how rapidly resistance mechanisms can evolve. These enzymes were discovered in few isolates in the late 1980s. They have now reached significant levels in hospitals and the community worldwide. Different ESBL enzyme variants (TEM, SHV, CTX-M) have been identified. They now substantially impair the utility of the later generation of cephalosporins and narrow the therapy options for patients with Gram-negative infections. Recently, reports on the wide dissemination of ESBL-producing bacteria in newborns, livestock, and in food accumulated. Meanwhile the worldwide dissemination of particular ESBL variants in epidemiologically successful Enterobacteriaceae strains has occurred.