Acid–base disorders are common in pediatric patients. We present a simple methodology for assessing both simple and complex acid–base disorders that is applicable to patients of all ages, and focus specifically on the usefulness of this approach in the pediatric patient. The application of four simple rules in sequence will define even the most complicated acid–base disturbance. However, because acid–base disorders are manifestations of systemic disorders, the primary value of characterizing them is that each generates a unique differential diagnosis. For each of the cardinal acid base disorders, the common and clinically-relevant causes in pediatric patients are explored. Additional diagnostic tools (including the serum anion gap, the delta–delta, the alveolar-arterial gradient, urine anion gap, and urine chloride), certain easily-recalled mnemonics, and empiric rules of thumb are also useful in specific situations. The treatment of acid–base disturbances is also considered, though treatment is generally best directed at the underlying disorder.