Acetate is used during regular hemodialysis to replace the bicarbonate lost during dialysis. The temporal changes of plasma bicarbonate and acetate concentrations and the critical role of acetate metabolism for the maintenance of plasma bicarbonate are described. We point out that the maximal rate of acetate oxidation in man is usually reached during dialysis, and we identify physiologic and pathologic factors that may modify this Vmax. A syndrome of ‘intolerance to acetate’ has been described. This syndrome is analyzed in the light of the metabolic consequences of a rapid flux of acetate oxidation in liver and muscle cells. More specifically, the effects of rapid acetate metabolism on tissue ATP, CoA, adenosine and other ATP degradation products are presented. The possible impact of dialysis-induced depletion of carnitine on optimal acetate metabolism is discussed. The potential clinical consequences produced by these changes are presented in relation to the symptoms sometimes observed during dialysis against acetate: vasodilation, hypotension and angina pectoris. The hypoxemia induced by acetate is also briefly reviewed. Different directions are proposed for future resea