This chapter describes the most widely studied and well-characterized cell lines in neuroscience research, and their applications and important results of those studies. In addition, several glial cell lines derived from glioma or glioblastoma have also been established and characterized. An important objective and envision of developing neuronal cell lines in those early days was to generate mass quantities of a particular type of cells or cells carrying certain specific genes for clinical transplantation with the purpose to repair or cure neurological disorders. The F98 and RG2 cell lines were produced in the same laboratory in 1971. F98 and RG2 cell lines have been used for a variety of in vivo transplantation studies including vascular permeability, regional blood flow, tumor metabolism, tumor growth, and blood brain barrier disruption, chemo-, radiation-, and gene-therapy. Available neural cell lines have provided relatively simple and well-controlled systems for elucidating basic biological processes and mechanisms governing neural growth, differentiation, signal transduction, and cell death.