Patients with renal or liver failure have a high risk of developing adverse effects of pharmacotherapy, since they are usually treated with many drugs and elimination of these drugs may be impaired. In this article, dose adjustment of the most important drugs used in these groups of patients is discussed. While clear guidelines for dose adjustment can be worked out for patients with renal failure this is more difficult for patients with liver failure since the metabolic capacity of the liver cannot be reliably quantified. Thus, despite dose adjustment, pharmacotherapy must be constantly monitored for adverse effects in these groups of patients.