Because of its effectiveness in curing infections caused by multi-drug resistant Gram-negative bacteria, polymyxin is applied to clinic again. Its drug resistance is generally low among a variety of antibiotics. However, there are studies showing that the drug resistance of polymyxin increases. As the last resort for treating multi-drug resistant Gram-negative bacteria, the occurrence of polymyxin resistance is especially important. This article summarizes the present situation, the underlying mechanism and the counteracting measure for polymyxin resistance so as to provide guidance for scientific and rational use of polymyxin in clinic, for controlling and reducing the dosage of polymyxin and for the measures in the prevention of spread and pervasion of polymyxin resistant Gram-negative bacteria.