Publisher Summary This chapter discusses an overview of a century of neuronal and neuroglial interactions, and their pathological implications. It also intends to exemplify interactions between neurons and glia (mostly astrocytes), primarily in pathological and clinical neurological contexts. Different work done by various scientists like Rudolph Virchow, Camillo Golgi, Mihily Lenhossek, Alois Alzheimer, Otfrid Foerster to name some are highlighted in this chapter. Rudolph Virchow had first described a connective or ground substance (“Bindesubstanz”) forming a sort of cement (“Kitt”) or neural glue (“Neuroglia”), in which the nerve elements are immersed. An example of the first type of astrocytic reaction is that associated with hepatic encephalopathy, as originally described by Alois Alzheimer. Involvement of neuroglia in several other neuropathological situations is briefly mentioned. Demyelination, especially in multiple sclerosis, is a major failure of the cooperative relationship between neuronal axons and their sheaths of myelin elaborated by oligodendroglia centrally and by Schwann cells peripherally. The neurological disorders as well as the many examples of brain and spinal cord injuries, focus attention on problems of reversal and functional repair of structures involved in such disabilities.