Peripherally acting mu-opioid receptor antagonists methylnaltrexone and alvimopan are a new class of drugs designed to reverse opioid-induced side-effects on the gastrointestinal system without compromising pain relief. This article gives an overview of the pharmacology, the efficacy, and adverse effects of these drugs. Both compounds seem to be generally well tolerated and effective for the treatment of opioid-related bowel dysfunction and postoperative ileus. Methylnaltrexone recently received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency for treatment of opioid-related bowel dysfunction in patients with advanced illness. Alvimopan was recently approved by the FDA for treatment of postoperative ileus, but the use of the drug is restricted to inpatients because it has been associated with an increased rate of myocardial infarction. Further research should assess the effectiveness and safety of these drugs in clinical practice.