Neurodegenerative diseases are characterized by the irreversible loss of neurons involved in networks, important for specific physiological functions. At present, several renewable cell sources stand in line to replace fetal brain cells as potential cell source for transplantation in the damaged brain. Recent developments raise the hope that selective populations of different neuronal phenotypes could be made "on demand". However, for every potential cell source there are still a lot of questions and drawbacks, which need to be resolved before a cell source could become the standard for clinical neuronal transplantation. The recent finding that the brain responds to damage by increased endogenous neurogenesis could prelude new "neurothrophic therapies", based on stimulating this endogenous repair. From preclinical studies it is evident that different disease mechanisms require different cell therapy approaches, depending on the underlying factor of the disease, the identity of neuronal systems that are involved and the complexity of networks that are affected. In this review the potential of different cell sources, including the endogenous progenitor cells, are discussed. Also results of preclinical and clinical transplantation studies in three different disease models are critically evaluated.