Polymyxin B is already being used extensively in the USA and other parts of the world; its use is likely to rapidly increase due to the greater burden of infections caused by MDR Gram-negative bacteria and the growing awareness of the limitations inherent in the clinical pharmacology of CMS/colistin. Cross resistance exists between the two polymyxins and thus both must be dosed optimally; but the recently generated scientifically-based dosage regimens for CMS/colistin cannot be extrapolated to polymyxin B. It is essential that an adequately powered study is conducted to define the clinical PK/PD/TD relationships of polymyxin B and identify, using next-generation proteomics, biomarkers for early detection of kidney injury. This will allow the development of scientifically-based dosage regimens for various categories of patients and an adaptive feedback control clinical tool for optimized dosing of polymyxin B in future individual patients.