The reasons causing a patient to be hospitalized in the ICU, the degree of organs involvement and the subsequent therapeutic interventions, are all elements that can interfere with the acid-base homeostasis. It may be difficult to correctly evaluate the disturbances of the acid-base balance and to understand the underlying physiopathological process. Though, it is crucial to clarify the steps that resulted in the alteration, in order to increase the probability of detecting the correct diagnosis and therapy. Two other elements make the understanding more complex first, it is difficult to estimate, even approximately, the degree of involvement of the 'structural' buffer systems (intracellular buffers, proteins, activation or inhibition of metabolic pathways, etc.) to calculate the total acid load and then quantify the bases necessary to restore the patient balance. Then, the disorder severity is too often assessed through the arterial blood gas analysis parameters, which limits observation to a restricted vascular area, and the disorder assessment to the bicarbonate-carbonic acid system.