Multidrug-resistant infections present a serious clinical and therapeutical problem. Colistin is an old-used polymyxin with rather poor pharmacokinetic profile and a remarkable nephrotoxicity. However, the emergence of multidrug-resistant bacteria has recently led to the increased use of colistin as a potentially available therapy. This article presents a 75-year-old diabetic woman with an early onset total knee arthroplasty infection by a multidrug-resistant Pseudomonas aeruginosa bacterial isolate that was managed successfully with surgical removal of the knee prosthesis, antibiotic impregnated cement and intravenous administration of colistin for 6 weeks, and second stage revision knee surgery. Two years later, laboratory and imaging studies showed no evidence of recurrence of infection.