Neurodegenerative diseases are an important yet incurable group of disorders of the nervous system. The idea that many of these disorders might be amenable to stem cell therapy is gaining momentum. A case can be made for stem cells in the replacement of either neurons or glia, though the common question of cell source remains paramount. The most likely sources for these cells are human embryonic stem cells (hESCs) or neural stem cells, with the differentiation of each toward the desired cell lineage. Other possible sources exist such as cells of the hematopoetic lineage (bone marrow or cord blood) but this remains controversial. Much of the impetus for stem cell therapy in the neurodegenerative diseases comes from clinical experiences in Parkinson's disease and ongoing experimental work on motor neuron replacement in amyotrophic lateral sclerosis, amongst others. Disorders of myelination, especially multiple sclerosis, would require replacement of myelinating glia and the cells that could be used to achieve this and their myelinating capacities in experimental animals will be discussed. In particular, I will discuss the differentiation of oligodendrocytes from hESCs and neural stem cells and their ability to make myelin on transplantation into different models of myelin disease. Stem cell therapy may be used not only to replace lost or dying cells, but also to modulate the disease milieu, thus broadening the potential scope of stem cells in disease treatment. (Supported by NMSS Grant TR 3761 and NIH Grant R01 055816)