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The kidney is able to rapidly eliminate many water-soluble xenobiotics (exogenous chemicals). However, in the face of extraordinary serum concentrations of these xenobiotics or renal dysfunction, alternative elimination techniques often become necessary. Extracorporeal removal (ECR) techniques are used to increase the clearance of xenobiotics. These techniques include hemodialysis (HD), charcoal hemoperfusion (HP), and modalities grouped under the heading of continuous renal replacement therapy (CRRT): continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Extracorporeal removal is limited to patients with significant or potentially significant clinical poisoning because the resources required to perform ECR are great. Therefore, most patients who are treated with these techniques are being cared for in intensive care units (ICUs). Our goal in this review is to discuss the properties that make xenobiotics amenable to removal by ECR and the advantages and disadvantages of the individual techniques. We discuss xenobiotics that constitute clear indications for ECR, including the toxic alcohols, salicylates, and lithium. We review the use of CRRT, a modality for which clear indications for treatment of poisonings are currently lacking.