Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells, mesenchymal stem cells and neural stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. Recently we have generated continuously dividing immortalized cell lines of human NSCs by introduction of v-myc oncogenes and these immortalized NSC lines have advantageous characteristics for basic studies on neural development and cell replacement therapy or gene therapy studies. Immortalized human NSCs were genetically manipulated in vitro, survive, integrate into host tissues and differentiate into both neurons and glial cells after transplantation to the intact or damaged animal brain. Both in vivo and in vitro human NSCs were able to differentiate into neurons and glial cells and populate the developing or degenerating CNS. Cell replacement and gene transfer to the diseased or injured CNS using NSCs have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases including Parkinson disease (PD), Huntington disease (HD), Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury and brain tumors. Steady and solid progress in stem cell research in both basic and pre-clinical settings should support the hope for development of stem cell-based therapies for neurodegenerative diseases.