Current standard of care treatments for neurodegenerative disorders such as Parkinson’s disease palliate symptoms but do not modify the course of the disease, and effects wane as the disease progresses. Innovation is needed to improve symptom management in advanced Parkinson’s disease. Gene therapy is an emerging treatment strategy for previously untreatable neurodegenerative disorders. Underlying the emergence of gene therapy as a viable therapeutic approach is the convergence of advances in key technologies, including an improved understanding of the genetic and molecular basis of disease, improved surgical techniques allowing precise delivery of viral vector gene therapy to specific central nervous system target(s) and better prediction of viral vector dissemination and transport during and after delivery. Importantly, gene therapy offers durable effect with a one-time treatment. Gene therapy strategies in Parkinson’s disease have included enzyme supplementation aimed at increasing dopamine synthesis and neurorestoration through increase in neurotrophic factors. In this chapter, clinical efforts in gene therapy involving enzyme replacement with aromatic L-amino acid decarboxylase (AADC) are reviewed. Other chapters focus on gene therapy for alternative enzyme replacement strategies (glutamic acid decarboxylase (GAD)) and gene therapy for neurorestoration, such as delivery of glial-derived neurotrophic factor (GDNF) or neurturin (NTN) transgenes, and are not discussed here.