The development of kinase inhibitors for disease relevant pathways has been complicated by the necessary specificity to retain safety, redundancy of kinases leading to lack of efficacy, and difficulties in overcoming the blood-brain barrier. The field of modulating phosphatases has the potential to overcome some of these issues and provide the next generation of therapeutic targets for Parkinson's Disease (PD). In this review in which M.Mouradian M.D of Rutgers-Robert wood Johnson Medical School was a collaborator, Signum addresses the phosphorylation pathways involved in PD, the kinases and issues related to their inhibition, and the evolving field of the phosphatases relevant in PD and how they may be targeted pharmacologically.