Parkinson's disease is characterized by progressive slowness in activities of daily living and is the most common cause of parkinsonism, whose symptoms include resting tremor, cogwheel rigidity, and bradykinesia. The introduction of levodopa and its positive effect on motor dysfunction in Parkinson's disease has allowed neurologists to focus on motor fluctuations. "End-of-dose wearing-off" and "morning akinesia" are terms to describe the transition between a patient's relatively normal motor performance when levodopa is effective and when it has transiently lost its effect on motor responses and parkinsonian symptoms reemerge. The choices available to alleviate these motor fluctuations range from altering the patient's levodopa/carbidopa dosing schedule to the addition of other agents to the regimen, including dopamine receptor agonists, catechol-O-methyltransferase inhibitors, monoamine oxidase inhibitors, and amantadine, as well as implementing dietary changes. Therapeutic decisions can be difficult because older agents have not been compared in head-to-head trials to determine which drugs are better than others and the order in which they should be tried or added to the levodopa regimen; however, all of the available treatments provide a good possibility of benefit to the patient. Deep brain stimulation surgery is an option for patients with medically intractable severe motor fluctuations.