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Continuous renal replacement therapy is increasingly used in the management of acute kidney injury in critically ill patients. The potential extracorporeal removal of drugs, in particular the removal of antimicrobials, is a concern to many clinicians. The results of clinical studies cannot be generalized because different treatment modalities and settings are used in heterogeneous patient populations. This review aims to provide general guidelines for drug dosing during continuous renal replacement therapy.The basic principles underlying drug removal with different modalities of continuous renal replacement therapy are reviewed and general approaches for drug dosage adaptation are proposed. Dosing should consider extracorporeal clearance, mainly depending on the dose and mode of therapy, type of membrane and protein binding, but also fractional extracorporeal clearance, accounting for hepatic, metabolic and residual renal clearance. Of note, pharmacokinetic variables may be highly variable in the critically ill. Appropriate dosing of antimicrobials additionally requires the application of pharmacodynamic principles. For nontoxic antimicrobials, the clinician should prefer slight overdosing, while monitoring of plasma concentrations is crucial for drugs with a narrow therapeutic index.Drug dosage adaptation during continuous renal replacement therapy can use several approaches, which all include a degree of unpredictability and thus require maximal reliance on drug monitoring.