Metabolic acidaemia (pH < 7.35 not primarily related to hypoventilation) is common amongst the critically ill and it is essential that clinicians caring for such patients have an understanding of the common causes. The exclusive elimination routes of volatile (carbon dioxide), organic (lactic and ketone) and inorganic (phosphate and sulphate) acids mean compensation for a defect in any one is limited and requires separate provision during critical illness. We discuss the models available to diagnose metabolic acidosis including CO2/HCO3(-) and physical chemistry-derived (Stewart or Fencl-Stewart) approaches, but we propose that the base excess and anion gap, corrected for hypoalbuminaemia and iatrogenic hyperchloraemia, remain most appropriate for clinical usage. Finally we provide some tips for interpreting respiratory responses to metabolic acidosis and how to reach a working diagnosis, the consequences of which are considered in Part 2 of this review.