The emergence of gram-negative bacteria resistant to most available antibiotics has led to the readministration of polymyxins B and E (colistin) as "salvage" therapy in critically ill patients. Recent studies demonstrated acceptable effectiveness and considerably less toxicity than reported in older studies of polymyxins. These old antibiotics may be administered for the treatment of intensive care unit-acquired infections of various types, including ventilator-associated pneumonia, urinary tract infections, bacteremia, and meningitis caused by multidrug resistant gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter species. Randomized controlled trials are urgently needed to further clarify various issues regarding the effectiveness and safety of polymyxins, however.