Tolcapone (Tasmar), an inhibitor of catechol-O-methyltransferase, is an effective antiparkinsonian agent when used as an adjunct to levodopa in patients with Parkinson disease who have end-of-dose motor fluctuations. In clinical trials, tolcapone significantly reduced "off" time and levodopa requirements. The drug is generally well tolerated, with the most common adverse events being dopaminergic related. However, clinical trials demonstrated dose-related increases in liver enzymes, and postmarketing surveillance noted 4 cases of acute hepatotoxicity with 3 fatalities that were attributed to tolcapone. For this reason, the drug was withdrawn from the market in some countries, and its use was severely restricted in the United States. An analysis of safety data indicates that, since the labeling restrictions in 1998, there have been more than 40,000 patient-years of tolcapone treatment worldwide, with only 3 reports of severe, but reversible, liver injury and no reports of hepatic fatality. It can be concluded that severe liver injury due to tolcapone is a rare event. Based on these data, the drug has been reintroduced to the market in several European countries, and the Food and Drug Administration in the United States has modified monitoring requirements. The new labeling recommends monitoring of liver function every 2 to 4 weeks for 6 months and at the physician's discretion thereafter. In addition, patients must be taken off the drug if blood tests show enzyme elevation of greater than twice the upper limit of normal. This article reviews the data pertaining to the safety and efficacy of tolcapone.