The hope that cell transplantation therapies will provide an ideal treatment option for neurodegenerative diseases has been considerably revived with the remarkable advancements in genetic engineering towards active cell fate determination in vitro. However, for disorders such as Huntington's disease (HD), the challenges that we face are still enormous. This autosomal dominant genetic disorder leads, in part, to massive neuronal loss and severe brain atrophy which, despite the cell type used, cannot be easily repaired. And before large clinical trials are even considered, we must take a critical look at the outcomes of the pilot studies already available, not only from a clinical perspective but also by a careful assessment of what we can learn from the autopsies of HD patients who have undergone transplantation. In this review, we summarize and discuss the seven transplantation pilot trials that were initiated worldwide in HD patients more than a decade ago, with a particular emphasis on the post-mortem analyses of nine unique cases. Moreover, we describe a series of factors, both technical and related to patient selection, that we deem important to predict the outcome of cell grafts in HD therapy.