Fernando Pagan, MD; Jason Aldred, MD, FAAN; Maria Cristina Ospina, MD; and Rajeev Kumar, MD, discuss how to navigate the complexities of choosing the most effective pharmacological and nonpharmacological treatment regimens for patients with advanced Parkinson disease, considering the evolving challenges and needs as the disease progresses, the impact on quality of life, and the incorporation of emerging therapies such as continuous subcutaneous infusion systems.