During the past 7 years, five new drugs have been approved by the United States Food and Drug Administration for the treatment of advanced Parkinson’s disease (PD). These advances in therapy have centered on the development of non-ergot dopamine agonists (pramipexole and ropinirole) and a new class of agents, catechol- O -methyltransferase (COMT) inhibitors (tolcapone and entacapone). The fifth agent, carbidopa/levodopa/entacapone, is a combined tablet that is the equivalent of taking one tablet each of carbidopa/levodopa and entacapone. Although these agents have been demonstrated to provide marked benefit to patients with parkinsonism, they do not represent major changes from previous treatments. In the case of the non-ergot agonists, the risk for rare fibrotic side effects does appear to be less (although the issue is still not settled), but their use has led to the occurrence of more common side effects, particularly sleep disorders and leg swelling. In addition, the improvement of motor fluctuations appears to be similar to that after use of the ergot agents available in the previous decade. In the case of COMT inhibition, these drugs simply alter the pharmacokinetics of levodopa and have no antiparkinsonian effect by themselves. Tolcapone has demonstrated a robust ability to lessen “off” time to a greater degree than other such agents, but its use has been limited because of …