The serum (plasma) anion gap is a useful additional piece of clinical information that can be easily derived without cost from the results of the most commonly requested biochemical profile, urea and electrolytes (U&E). It is the difference between the sum of measured anions (chloride and bicarbonate) and the sum of the measured cations (sodium and potassium) and is normally of the order of 12 ± 4 mmol/L. Pathological causes for both decreased and increased anion gap have been identified but increased anion gap is far more common than decreased anion gap and is usually the result of metabolic acidosis. This underscores the principal clinical utility of the anion gap, which is the evaluation of patients suffering disturbance of acid-base balance. In a recently published comprehensive review the authors describe just how the serum (plasma) anion gap is used to elucidate acid-base disturbances. Following a brief overview of the concept of the anion gap there is extensive discussion of the distinction between normal anion gap metabolic acidosis and high anion gap metabolic acidosis. The discussion includes consideration of the delta gap and delta ratio, two parameters derived from the anion gap that are useful in distinguishing metabolic acidosis from mixed acid-base disturbance (metabolic acidosis and respiratory alkalosis). Other topics considered include the important effect that reduced serum albumin can have on anion gap, the causes of the rarely encountered negative anion gap, and the clinical utility of calculating urine anion gap. The review includes some helpful clinical vignettes that illustrate practical clinical use of the anion gap. A useful complementary editorial discusses the limitations of the anion gap as a diagnostic tool.