Recently, the metabolic routes for acetone metabolism have been described. Therefore, acetone cannot further be regarded as a waste product of metabolism. However, its physiological role in biochemical machinery is not clear. Here, an integrative model for the role of acetone metabolism is presented that orders the events occurring in acetonemia in sequence: (i) acetone participates in pH regulation; and (ii) acetone degradation in the liver both contributes to glucostatic function of the liver and provides C3 fragments to peripheral tissues as additional fuel. The model raises a novel approach to the study of the physiological role of acetone metabolism.