Overview.- Multidrug resistant Gram-negative pathogens: the urgent need for 'old' polymyxins.- Discovery, antibacterial spectrum and chemistry.- Mechanisms of antibacterial activity.- Mechanisms of resistance.- Bioanalysis and stability of polymyxins.- In vitro pharmacodynamics and PK/PD in animals.- Antibacterial susceptibility breakpoints.- Labeling of parenteral products of colistin methanesulfonate.- Meta-analysis of polymyxin use in patients.- Clinical use of colistin.- Clinical use of polymyxin B.- Pharmacokinetics, pharmacodynamics, toxicodynamics and dosing recommendations.- Rational combinations with other antibiotics.- Toxicities in patients: management and mechanisms.- Antiendotoxin effect.- Discovery of novel polymyxin-like antibiotics.- Conclusion.