The hallmark of metabolic alterations in acute renal failure (ARF) is accelerated protein breakdown which, unfortunately, cannot be suppressed effectively by provision of exogenous nutritional substrates. Causes of excessive protein catabolism are manifold and present a combination of unspecific mechanisms induced by the acute disease process and underlying illness or associated complications, effects induced by the acute loss of renal function and, finally, the type and intensity of renal replacement therapy. Specific uremic toxic effects, insulin resistance, hormonal derangements, metabolic acidosis, circulating proteases, inflammatory mediators, and dialysis-related losses of nutritional substrates all contribute to the activation of protein degradation. Metabolism in ARF is also affected by an impairment of the multiple metabolic and endocrine functions of the kidney. Various amino acids are synthesized or interconverted by the kidneys and may become conditionally indispensable. The kidney is also an important organ in the degradation of peptides, such as peptide hormones. As a consequence of these metabolic aberrations, imbalances in amino acid pools in plasma and in the intracellular compartment occur in ARF and elimination and utilization of infused amino acids is altered. Protein or amino acids requirements are influenced more by the nature of the illness causing ARF, by the extent of hypercatabolism, by associated complications, and by the type and frequency of renal replacement therapy than by renal dysfunction per se. In noncatabolic patients, an intake of 1 g/kg body weight per day may be sufficient, while in critically ill hypercatabolic patients undergoing continuous renal replacement therapy, 1.5 g amino acids/kg body weight per day should be provided to minimize nitrogen losses. For the future, we need to identify safe methods to control the accelerated catabolism in order to improve the efficiency of nutritional interventions in patients with ARF.