Acid-base disorders are prevalent in critically ill patients, and a systematic approach is essential for evaluation. The first step is to determine the primary process based on a patient's pH, partial pressure of carbon dioxide, and bicarbonate measurements. After this is complete, the next step is to evaluate for respiratory or metabolic compensation. Deviations from expected compensation may indicate additional acid-base processes. For metabolic acidosis, anion gap calculation distinguishes between anion gap metabolic acidosis and non–anion gap metabolic acidosis. The evaluation for anion gap metabolic acidosis includes calculating the osmolal gap and conducting a gap-gap analysis. Evaluating non–anion gap metabolic acidosis involves urine anion gap calculation. These analyses identify potential etiologies and additional acid-base disturbances. Metabolic alkalosis assessment begins with measuring urine chloride levels to determine whether the process is a result of chloride depletion. Respiratory acidosis, caused by hypoventilation, often results from chronic lung disease or neuromuscular dysfunction. Respiratory alkalosis, due to hyperventilation, is common in sepsis, chronic liver disease, and acute pulmonary embolism.