Colistin is an antibiotic of last resort, works as a last line of defense against illness caused by the multiple drug resistant (MDR) gram negative bacteria. Polimixins consist of aqua phobic acyl tail, linear tripeptide part, and heptapeptide ring. Chemical formula of colistin is C52H98N16O13. Colistin is given in two forms, colistin methane sulfonate (CMS) and colistin sulfate.
 Findings: Colistin disturbs or destroys the outer membrane of bacteria, or stops the respiratory enzymes of the inner membrane of bacteria. Colistin also works as an antiendotoxin. Colistin has great bactericidal activity against gram negative rods. Colistin resistance is a serious concern of present time. High rate of the spread of MDR gram negative bacterial infections is leading to high use of colistin for treatment, due to which prevalence of colistin resistance is increasing worldwide. As bacterial outer membrane is the main target of colistin, resistance against it develop by modification of outer membrane LPS. There are several mechanisms of colistin resistance. Intrinsic mechanism involves expression of arnBCADTEF operon and eptB gene. Acquired non-transferable resistance involves pmrAB, PhoPQ, and CrrAB two component systems (TCSs), mgrB gene and ramA. Transferable resistance is more serious concern as it can be spread in population by horizontal gene transfer. Mcr genes are responsible for transferable or plasmid-mediated colistin resistance.
 Conclusion: This review focuses on the chemistry of colistin, mechanism of action, spectrum of action, colistin resistance and different mechanisms behind it.