The use of stem cells for neuroreplacement therapy is no longer science fiction--it is science fact. We have succeeded in the development of neural and mesenchymal stem cell transplantation to produce neural cells in the brain. We have also seen improvement in cognitive function following stem cell transplantation in a memory-impaired aged animal model. These results promise a bright future for stem cell therapies in neurodegenerative diseases. Before we begin to think about clinical applications beyond the present preclinical studies, we have to consider the pathophysiological environment of individual diseases and weigh the factors that affect stem cell biology. Here, I not only review potential therapeutic applications of stem cell strategies in neurodegenerative diseases, but also discuss stem cell biology regarding factors that are altered under disease conditions.