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Publisher Summary This chapter presents a brief introduction to the family of glutamate receptors, which provide the principal means of fast-excitatory neurotransmission in the brain, and discusses their likely role in the progression of many neurodegenerative diseases. A hallmark of many neurodegenerative diseases is the extraordinary specificity through which they progress through the nervous system. Even in the severest forms of neurodegeneration, it is not uncommon to find that discrete regions of the brain are destroyed, while adjacent regions are spared. Neurotransmission in the brain involves the balanced activity of excitatory and inhibitory neurotransmitter receptor systems acting through ligand-activated ion channel receptors. Glutamate-activated ligand-gated ion channels (GluRs) are the primary receptors responsible for fast excitatory-neurotransmission in the brain and their activation is central to physiological processes associated with learning and memory. The chapter discusses the role of the immune system in neurologic diseases and the ways in which the specificity of the immune system can be utilized to explore the way the GluR family contributes to the etiology and regional specificity of neurodegenerative disease progression.