Background and Aims: The emergence of multidrug resistant strains of Gram-negative bacteria, especially the lactose nonfermenters like Pseudomonas and Acinetobacter, in the intensive care units have prompted renewed worldwide interest in the polymyxins. However, perceived nephrotoxicity has been a major vexation limiting their early and regular use in severe sepsis. This study was conducted to assess the safety and efficacy of polymyxin B in patients with severe sepsis and septic shock. Materials and Methods: Forty-five patients with sepsis admitted in our medical-surgical intensive care units were identified from pharmacy records to have received polymyxin B. We retrospectively reviewed the clinical and microbiologic outcomes as well as occurrence of renal failure temporally related to the use of intravenous polymyxin B. Results: polymyxin B was used in severe sepsis and septic shock with the isolated organism being resistant to other available antimicrobials or clinical deterioration despite carbapenem use. Overall mortality was 52% and among patients who received at least eight days of intravenous polymyxin B, 67% patients with initial septic shock and 62% with severe sepsis survived. The target multidrug resistant organism was cleared in 88% of subjects evaluated by repeat microbiologic testing. Acute renal failure developed in only two patients (4%). Conclusions: Polymyxin B has acceptable effectiveness against nosocomial multidrug resistant Gram-negative sepsis. The associated nephrotoxicity has been found to be significantly lower than previously reported even in patients with background renal impairment and established risk factors of renal failure.