Acidosis is a common clinical condition with both chronic and acute forms. Chronic metabolic acidosis induces an increase in protein degradation; however, its effects on protein synthesis are less clear. Metabolic acidosis increases net whole-body proteolysis by a massive increase in protein degradation and only a moderate increase in protein synthesis. Most studies in humans on the relation between acidosis and protein metabolism have concentrated on patients with chronic renal failure with metabolic acidosis. However, because chronic renal failure is associated with other abnormal metabolic conditions such as malnutrition, it is difficult to separate out the effects on protein metabolism solely due to acidosis. Data on the influence of other forms of acidosis, e.g., respiratory acidosis, diabetic ketoacidosis, and lactic acidosis, on protein turnover are sparse. Similarly, data about the influence of acidosis on the metabolism of other proteins, such as the liver-produced secretory proteins, are lacking. Future research should more vigorously investigate the influence of acidosis on protein metabolism in various clinical conditions and the potential regulatory effects on the metabolism of secretory proteins. The reversal of acidosis might prove to have beneficial effects on protein wasting, and thus decrease morbidity and possibly mortality.