OBJECTIVE: To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1967-June 2007) using the terms levodopa, wearing-off, and Parkinson's disease. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles that were identified from the data sources and written in English were evaluated. DATA SYNTHESIS: Levodopa is the most efficacious therapeutic agent in PD; however, the response of patients to levodopa changes over time. Eventually, the duration of response becomes shorter and more unpredictable, and complications emerge. One of the first complications observed with levodopa therapy is wearing-off, which can emerge within 1-3 years of initiation of levodopa treatment. Wearing-off is characterized by the predictable emergence of motor and nonmotor PD symptoms before the next scheduled dose of medication. Despite effective treatment options to tackle wearing-off, it remains underrecognized and under treated. With early identification and optimization of treatment, wearing-off can be managed effectively, resulting in improved quality of life for patients with PD. CONCLUSIONS: Owing to their training and accessibility, pharmacists play an increasingly important role in the management of patients with PD. Pharmacists are uniquely placed to identify wearing-off, offer timely advice, and facilitate the optimization of treatment regimens to improve patients' quality of life and enhance long-term outcomes.