Metallo-beta-lactamases (MBLs) are being reported with increasing frequency and from several countries worldwide and are becoming the prevalent and most clinically significant determinants of carbapenem resistance. Furthermore, MBL-producing strains that exhibit a pan-resistant phenotype are increasingly detected. Initially MBLs were detected in Pseudomonas aeruginosa, however nowadays they are frequently found in Acinetobacter baumannii, Klebsiella pneumoniae and other Enterobacteriaceae. MBLs spread easily on plasmids and cause nosocomial infections and outbreaks with excess mortality. Such infections mainly concern patients admitted to Intensive Care Units with several co-morbidities and a history of prolonged administration of antibiotics. MBL-producing strains exhibit resistance to almost all currently available antibiotics. In vitro studies reveal that tigecycline and colistin are the only antibacterial agents with consistent activity against MBL-producing strains. Randomised controlled trials are required in order to evaluate the available therapeutic regimens, including treatment combinations. Tigecycline and colistin should be used under appropriate prescribing practices. Surveillance to monitor the emergence of resistance to these agents as well as implementation of infection control measures should be strengthened. MBL inhibitors are urgently needed, however, none is in late pre-clinical development.