The traditional approach to evaluating acid-base balance uses the Henderson-Hasselbalch equation to categorize four primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), metabolic acidosis (decreased extracellular base excess), or metabolic alkalosis (increased extracellular base excess). The anion gap is calculated to detect the presence of unidentified anions in plasma. This approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are approximately normal; however, when their concentrations are markedly abnormal, the Henderson-Hasselbalch equation frequently provides erroneous conclusions as to the cause of an acid-base disturbance. Moreover, the Henderson-Hasselbalch approach is more descriptive than mechanistic. The new approach to evaluating acid-base balance uses the simplified strong ion model to categorize eight primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), strong ion acidosis (decreased [SID+]) or strong ion alkalosis (increased [SID+]), nonvolatile buffer ion acidosis (increased [ATOT]) or nonvolatile buffer ion alkalosis (decreased [ATOT]), and temperature acidosis (increased body temperature) or temperature alkalosis (decreased body temperature). The strong ion gap is calculated to detect the presence of unidentified anions in plasma. This simplified strong ion approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are markedly abnormal. The simplified strong ion approach is mechanistic and is therefore well suited for describing the cause of any acid-base disturbance. The new approach should therefore be valuable in a clinical setting and in research studies investigating acid-base balance. The presence of unmeasured strong ions in plasma or serum (such as lactate, ketoacids, and uremic anions) is best detected by calculating the SIG. The AG, actual bicarbonate concentration, and standard bicarbonate concentration all ignore the effects that changes in plasma protein and phosphate concentration have on plasma pH, thereby inevitably leading to inaccuracies in estimating the unmeasured strong ion concentration in plasma.