Colistin (polymyxin E) binds to the cell wall of gram-negative bacteria, leading to osmotic destruction of the cell. Since its introduction in 1959, colistin has been little used parenterally due to a high incidence of reversible nephrotoxicity and, to a lesser extent, neurotoxicity. Colistin use remained limited to combating Pseudomonas aeruginosa in cystic fibrosis patients. In addition, oral colistin is part of the recently introduced regime of selective digestive tract decontamination in ICU patients. Intravenous administration of colistin is now increasingly prescribed for the control of multi-resistant microorganisms. Colistin monotherapy, however, rapidly selects resistant subpopulations. Therefore, only combination therapy is advised. The prodrug colistimethate sodium is less toxic and is hydrolyzed in vivo to active colistin; colistin is renally cleared. Clinical practice remains hampered by lack of uniformity and standardization of names, dosage units, dosing recommendations and methods of concentration and susceptibility testing.