Extended-spectrum β-lactamase (ESBL)-producing organisms are a global problem. No randomized controlled trials have ever been performed to guide optimal treatment. However, in vitro studies and observational studies strongly suggest that carbapenems (imipenem or meropenem) should be regarded as drugs of choice for serious infections due to ESBL-producing organisms. Other β-lactam antibiotics (cefepime, β-lactam/β-lactamase inhibitor combinations) are not suitable as first-line therapy. The increasing frequency of the association between quinolone resistance and ESBL production have greatly limited the role of this class of antibiotic against ESBL producers.