Selegiline, a selective monoamine oxidase-B inhibitor, has been used for decades in the treatment of Parkinson's disease. The recent development of an orally disintegrating dosage form using Zydis technology allows pregastric drug absorption and, thus, greatly improving the pharmacodynamic and pharmacokinetic drug profiles. This new formulation provides higher drug bioavailability and a substantially reduced concentration of active metabolites. As an adjunct to levodopa, Zydis selegiline is shown to be a safe and effective therapy in patients with motor fluctuations and wearing off. This review outlines the advantages of a Zydis formulation in Parkinson's disease and the evidence supporting the use of Zydis selegiline for motor fluctuations.