Intra-striatal transplantation of homotypic fetal tissue at the time of peak striatal neurogenesis can provide some functional benefit to patients suffering from Huntington's disease. Currently, the only approach shown to slow down the course of this condition is replacement of the neurons primarily targeted in this disorder, although it has been transient and has only worked with a limited number of patients. Otherwise, this dominantly inherited neurodegenerative disease inevitably results in the progressive decline of motricity, cognition, and behavior, and leads to death within 15 to 20 years of onset. However, fetal neural cell therapy of Huntington's disease, as with a similar approach in Parkinson's disease, is marred with both technical and biological hurdles related to the source of grafting material. This heavily restricts the number of patients who can be treated. A substitute cell source is therefore needed, but must perform at least as well as fetal neural graft in terms of brain recovery and reconstruction, while overcoming its major obstacles. Human pluripotent stem cells (embryonic in origin or induced from adult cells through genetic reprogramming) have the potential to meet those challenges. In this review, the therapeutic potential in view of 4 major issues is identified during fetal cell therapy clinical trials: 1) logistics of graft procurement, 2) quality control of the cell preparation, 3) immunogenicity of the graft, and 4) safety of the procedure.