In order to assess acid-base disturbances in patients under various conditions, many schemes including the traditional bicarbonate-centered approach developed by Henderson and Hasselbalch, base-excess approach developed by Copenhagen group, and the physicochemical approach have been introduced. For almost 100 years, the most traditional Henderson–Hasselbalch equation has provided a simple relationship among the respiratory parameter (PCO2), the non-respiratory parameter bicarbonate (HCO3-) and the overall acidity parameter (pH) by considering bicarbonate one of the strongest buffers and determinants of pH in physiologic system. Although it is relatively easy to understand and to apply in clinical settings, the equation does not allow to quantify the severity of the metabolic derangements in the same way as the respiratory component and it does not tell clinicians about any acids other than carbonic acid. In order to separate metabolic and respiratory components in acid–base disorders, the concept of base-excess had been introduced. Blood base-excess measures the metabolic component that is independent from the respiratory component and incorporates the effect of hemoglobin as a buffer. Despite the conveniences of its application for everyday clinical practice, the base excess equation also suffers from inaccuracy with changes in PCO2, albumin or phosphate, and it is sometimes unable to detect complicated acid–base disorders or identify different types of metabolic acidosis. To overcome these limitations of the two traditional approaches, Stewart modeled solution that contained a complex mixture of ions of constant charge over the physiological pH range (strong ions), non-volatile proton donor/acceptors which transfer hydrogen within the physiological pH range (weak acid/base), and the volatile bicarbonate–CO2 buffer system. In this approach, there are three responsible variables to independently determine the dissociation of water, and consequently the hydrogen ion concentration, to maintain electrical neutrality. In spite of the advantage that it may help to clarify the underlying mechanisms of a number of acid-base problems frequently encountered in critically ill patients, this complex formula would be beyond the grasp of the average pupil. Furthermore, we need to bear in mind that the normal kidney’s remarkable response to subtle differences in pH or, more likely, intracellular CO2 does not take these differences into account. It is clear that traditional approaches and Stewart approach are complementary giving the similar information about the acid–base phenomena despite their different concepts and some inconsistent results between these approaches. The decision on which method will be used for any occasion is up to clinicians.