In this book, we present a discussion of the immune functions of neuroglia and their interactions with common infectious diseases in the brain. While most is known about microglia and astrocytes, as are extensively reviewed here, our understanding of other glia, including oligodendrocytes and ependymal cells, continues to grow in terms of their response to infection. Our discussion focuses on the most clinically relevant and well-studied infectious diseases, including Streptococcus pneumoniae, Neisseria meningitidis, and human immunodeficiency virus (HIV), among others, in their interactions with microglia and astrocytes. These immune responses within the central nervous system are crucial for protecting us from pathogens and yet must be carefully balanced with the need to protect brain structures that are sensitive to inflammatory damage. The complex interactions between pathogens and glia, as well as glia with other cells in the central nervous system, are an area of fascinating research that continues to grow as we attempt to translate our understanding of these processes to new treatment and prevention strategies.