From its initial conception, this special issue on stem cells was intended to showcase the potential therapeutic utilityof stem cells as well as to initiate scientific debate concerning the ability of stem cells to lead to viable tissueregeneration as well as functional plasticity in an organism during acute or chronic injury. In general, stem cellsbegin as undifferentiated cells, but have the ability to yield progeny cells that may lead to self-renewal, non-renewing progenitors, or terminally differentiated cells. Stem cells possess different capacities and are classifiedaccording to a particular cell type that they can produce, such as whether they are unipotent (one mature cell type),oligopotent (a restricted subset of cell lineages), multipotent (a broader range of a subset of cell lineages),pluripotent (embryo proper cells), or totipotent (embryonic and extra-embryonic cells). While we examine the scientific basis and therapeutic promise of stem cells in this issue, we must also be cognizantof the present hurdles facing stem cell research. Debates concerning the use of human embryonic stem cells haverecently been fueled with the recent publication that reports the derivation of a pluripotent embryonic stem cell linefrom a cloned human blastocyst (Hwang, WS et al., 2004). Yet, prior to the consideration of any clinicalapplications for stem cells in regards to human disease, significant additional studies are required on several frontsas follows: (1) to understand the cellular mechanisms that regulate the differentiation of animal and human tissues;(2) to elucidate how differentiated cells may be targeted to specific tissues for repair; and (3) to prevent the possibledevelopment of further injury in damaged tissue during stem cell applications, such as by the potential generation ofneoplastic cells from undifferentiated stem cells. These challenges can be overcome with the p roper support in aclimate that requires continual reassurance and education to allay any fears that specific ethical concerns will not bebreached. Timely additional work that reports the availability of seventeen new embryonic stem cell lines thatreproducibly differentiate in vitro and in vivo into cell types from all three embryonic germ layers (Cowan, CA etal., 2004) (barred at this time from use in work funded by United States federal sources) further assists us inunderstanding the potential of stem cells for treating human disease. As we move forward, it is our intention that highlighting both the accomplishments achieved as well as theobstacles to be overcome in stem cell research will bring both the scientific community and the public closer toobjectively assessing the potential promise of stem cells for the treatment of clinical disease. In the series ofmanuscripts that follows, the role of stem cells from various sources are discussed as well as their developmentalcapacity for “transdifferentiation”, the transition of a cell from a specific tissue lineage into a different tissuelineage. Our Guest Editor, Dr. Feng C. Zhou, has performed an exemplary job in assembling an outstanding groupof contributors for this issue to provide an overview and platform for present and future considerations of thepotential role of stem cells to treat human disease, especially those that involve neurodegenerative disorders.