As a consequence of antibiotic overuse and misuse, nosocomial infections caused by multidrug-resistant bacteria represent a physician's nightmare throughout the world. No newer antimicrobials active against Pseudomonas aeruginosa, the main multidrug-resistant nosocomial pathogen, are available or under investigation. The only exceptions are linezolid, some newer glycopeptides (dalbavancin, oritavancin and telavancin) and daptomycin (a lipopeptide), which are active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains, as well as tigecycline, a potent in vitro glycylcycline against MRSA, VRE, Acinetobacter baumannii and entended-spectrum β-lactamase (ESBL)+ Enterobacteriaceae. Colistin, an antibiotic of the 1950s has been rediscovered by intensive care unit physicians for use against ESBL+ Enterobacteriaceae, as well as against multidrug-resistant P. aeruginosa and A. baumannii isolates. Although success rates with colistin range between 50 and 73%, almost all studies are retrospective. Immunostimulation efforts against S. aureus are still under development. As antibiotic research and development stagnate, rational policies for prescribing existing antibiotics plus strict infection control are the current mainstay efforts for preventing and combating multidrug-resistant bacterial infections.