The spectrum of available therapeutic options has become drastically narrowed in recent years, particularly for nosocomial multidrug-resistant gram-negative pathogens. This therapeutic void has created a resurgence of interest in colistin. In 5 published series since 1999, clinical response rates for pneumonia due to Pseudomonas aeruginosa or Acinetobacter baumannii treated with intravenous colistin have ranged from 25% to 62%, despite high severity of illness at baseline. De novo nephrotoxicity was observed in 8%-36% of patients, despite close attention to both appropriate dosing and duration of treatment. Neurotoxicity, which was commonly described in the old colistin era, has been exceedingly rare in recent experience. Aerosolized therapy as an adjunct to systemic treatment appears promising, but the current published data are much too limited to allow determination of the incremental benefit of the addition of aerosolized treatment to systemic treatment. Colistin is a reasonably safe last-line therapeutic alternative for pneumonia due to multi- or panresistant P. aeruginosa or A. baumannii.