Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.