Severe infection frequently necessitates admission to the intensive care unit (ICU). Equally, nosocomial sepsis often complicates the clinical course in ICU.  Early, appropriate application of antibiotic therapy remains a cornerstone of effective management. However, this is challenging in the critical care environment, given the significant changes in patient physiology and organ function frequently encountered. Being cognisant of these factors, prescribers need to consider modified dosing regimens, not only to ensure adequate drug exposure, and therefore the greatest chance of clinical cure, but also to avoid encouraging drug resistance.