ObjectiveTo review the physiology of the chloride ion and its relationship to various disease states encountered in the ICU. Special emphasis was paid to the renal handling of chloride and its role in the evaluation of the urine and serum anion gaps. Metabolic acidosis and alkalosis are discussed.Data SourcesEnglish-language articles were identified through a search of the MEDLINE and Index Medicus databases. Bibliographies of retrieved articles were examined for relevant articles.Study SelectionApproximately 125 articles and 25 textbook chapters were reviewed. Those articles most applicable to the ICU were used. Information contained in text chapters was included primarily in the tables.Data ExtractionAll available information was reviewed and analyzed by the authors before inclusion.Data SynthesisGuidelines for the evaluation of urine and serum electrolyte concentrations are presented. The use of the urine anion gap is discussed, particularly as it relates to the diagnosis of hyperchloremic metabolic acidosis. Stool chloride provides information relevant to congenital and acquired diarrheas. The evaluation of metabolic acidosis requires the calculation of the serum anion gap. Both normal and increased gap acidoses are discussed, although increased gap acidoses are more commonly encountered in the ICU. Urine chloride is invaluable in defining whether the metabolic alkalosis is sodium-chloride responsive (urine chlorideConclusionsMeasurement of chloride is a valuable tool in the evaluation and treatment of a variety of disorders. Serum chloride is most helpful in assessing both normal and increased anion gap metabolic acidoses, while urine chloride finds utility in the diagnosis of metabolic alkalosis and hyperchloremia metabolic acidosis. The evaluation of any disturbance in chloride homeostasis that defies easy explanation necessitates the measurement of stool electrolytes.