Renal failure has been defined functionally, and the term acute kidney injury (AKI) has been coined to describe progressive grades of functional abnormality. AKI is common in critically ill patients with sepsis. Recognition of possible AKI is important as it must be accompanied by measurement of creatinine clearance to facilitate appropriate antibacterial dosing in critically ill septic patients. Conversely, awareness of the increased incidence of augmented renal clearance in subgroups of critically ill patients (e.g., resuscitated trauma, major surgical and burns patients) should lead to confirmatory measurement of creatinine clearance, and if indicated, dose adjustment. In addition, sepsis and AKI are associated with marked physiological alterations that are often associated with unrecognized pharmacokinetic changes. A thorough understanding of pharmacokinetic principles and organ function in the critically ill patients with AKI is required to guide appropriate dosing, both experimantally and in clinical practice. This pharmacokinetic knowedge should be utilised to achieve appropriate pharmacodynamic targets. A method of individualized antibacterial dosing, based on a dataset derived from published data in the critically ill receiving, is proposed whereby the patient’s dose should be derived from a dataset chosen by matching as far as possible the severity of illness, organ failure, and modes of support used. The use of therapeutic drug monitoring (TDM) informed by population-based pharmacokinetic (PK) data in critically ill patients offers further promise for the optimization of antibacterial dosing.