Polymyxins are old antimicrobials, discontinued for many years because of nephrotoxicity and neurotoxicity reports and reintroduced recently due to the increasing frequency of multiresistant Gram-negative bacterial infections. There are very few data related to toxicity and efficacy from transplanted patients, the major subjects of this study. All solid-organ-transplanted patients from our institution during January 2001 to December 2007 who used polymyxins were retrospectively assessed for nephrotoxicity and treatment efficacy. Microbiological and clinical cure rates were 100% and 77.2%, respectively. Only transplant patients subjected to at least 72 h of intravenous polymyxin were entered in the study. Overall, 92 transplant patients were included, and the nephrotoxicity rate was 32.6%. Multivariate analysis showed a statistically significant association between duration of polymyxin treatment (P = 0.037; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.12) and significant renal dysfunction. Polymyxin use is associated with very high rates of significant decrease in renal function; therefore, polymyxin must be used only when no other option is available and for as briefly as possible in the solid organ transplant setting.