The presence of stem and progenitor cells in the adult human brain suggests a putative and persistent role in reparative behaviors following neurological injury and neurological disease. Too few stem/progenitor cells (as in the case of Parkinson's disease) or too many of these cells (as in the case of Huntington's disease and glioma) could contribute to and even signal brain pathology. We address here critical issues faced by the field of stem cell biology and regenerative medicine, arguing from well-documented as well as speculative perspectives for a potential role for stem cells in the pathology of many human neurological diseases. Although stem cell responses may result in regenerative failure, in many cases they may help in the establishment or re-establishment of a functional neural circuitry (eg, after stroke). Therefore, we would argue that stem cells have a crucial-either positive or negative-role in the pathology of many neurological diseases.