The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.