The development of cell-based therapies aimed to promote tissue repair in central nervous system (CNS) diseases, represents one of the most challenging areas of investigation in the field of regenerative medicine. Several cell-replacement strategies have been developed in the last few years. Recent evidence from our and other labs indicates that undifferentiated neural stem/precursor cells (NPCs) might very efficiently protect the CNS from chronic degeneration induced by inflammation both in small rodents as well as in primates (Nature 2003, 422: 688-694; Nature 2005, 436: 266-271; Stem Cells 2007, 5: 2583-2592; Ann Neurol, in the press). However, before envisaging any potential human applications of such therapies we need to confront with some preliminary and still unsolved questions: (*) the ideal stem cell source for transplantation; (*) the ideal route of cell administration; (*) the differentiation and persistence of stem cells into the targeted tissue and – last but not least – (*) the functional and long-lasting integration of transplanted cells into the host tissue (Nat Rev Neurosci 2006, 7: 395-406). Current projects in the laboratory are further exploring the cellular and molecular mechanisms regulating the therapeutic plasticity of NPCs in inflammatory CNS diseases such as multiple sclerosis, ischemic stroke and spinal cord injury (Nat Rev Neurosci 2006, 7: 395-406; Proc Natl Acad Sci U S A 2006, 103: 13174-13179).