Microglia are a heterogeneous population of tissue macrophages in the central nervous system (CNS), orchestrating a variety of functions ranging from neurogenesis, synaptogenesis, and network morphogenesis to immune sensing, surveillance, and defense. A growing body of evidence shows an unequivocal implication of microglia in many neurodegenerative disorders, including Parkinson’s disease (PD). With the recent advent of novel high-throughput technologies and single-cell techniques, as well as high-resolution molecular analyses, new microglia expression profiles, versatile phenotypes, and signaling pathways linked to PD pathology have been identified. Characterization of the microglia’s role in PD pathology is a crucial milestone to model individual disease trajectories and advance personalized therapeutic strategies. Therefore, the aim of this chapter is to provide an overview of microglia implications in PD pathology. First, the physiological and pathophysiological roles of microglia as well as their context-dependent phenotypic diversity in PD are introduced. Next, the activation pathways of microglia-mediated inflammation along with the genetic and molecular signatures of microglia-mediated degeneration are described. Finally, opportunities for microglia targeting as potential therapeutic options are discussed.