© 2014 Springer Science+Business Media New York. All rights reserved. Astrocytes, the most abundant cell in the central nervous system, are essential for brain function and homeostasis. This chapter focuses on the immunological role of astrocytes in the pathology of major neurodegenerative diseases. Astrocyte activation, or astrogliosis, has been observed in many neurodegenerative diseases. Factors associated with neurodegeneration including extracellular oligomerized proteins such as amyloid β and α-synuclein as well as inflammatory cytokines and chemokines can influence the functionality of astrocytes. In response to such stimuli, astrocytes produce a multitude of soluble factors including cytokines, chemokines, reactive oxygen/nitrogen species, and growth factors. This astrocytic response is initially protective, limiting damage and promoting functional recovery. However, the prolonged and progressive nature of neurodegenerative diseases establishes an environment in which astrogliosis may be aberrantly sustained, and the ongoing production of astrocyte-derived molecules contributes to the non-resolving inflammatory and neurotoxic landscape associated with neurodegeneration.