The rapid and irrepressible increase in antimicrobial resistance of pathogenic bacteria that has been observed over the last two decades is widely accepted to be one of the major problems of human medicine today. Several aspects of this situation are especially worrying. There are resistance mechanisms that eliminate the use of last-choice antibiotics in the treatment of various kinds of infection. Many resistance mechanisms that emerge and spread in bacterial populations are those of wide activity spectra, which compromise all or a majority of drugs belonging to a given therapeutic group. Some mechanisms of great clinical importance require specific detection procedures, as they may not confer clear resistance in vitro on the basis of the interpretive criteria used in standard susceptibility testing. Finally, multiple mechanisms affecting the same and/or different groups of antimicrobials coexist and are even co-selected in more and more strains of pathogenic bacteria. The variety of β-lactamases with wide spectra of substrate specificity illustrates very well all the phenomena mentioned above. Being able to hydrolyze the majority of β-lactams that are currently in use, together they constitute the most important resistance mechanism of Gram-negative rods. Three major groups of these enzymes are usually distinguished, class C cephalosporinases (AmpC), extended-spectrum β-lactamases (ESBLs) and different types of β-lactamases with carbapenemase activity, of which the so-called class B metallo-β-lactamases (MBLs) are of the greatest concern. This review is focused on various aspects of the evolution and epidemiology of ESBLs; it does not cover the problems of ESBL detection and clinical relevance of infections caused by ESBL-producing organisms.