Previous open-label clinical trials have provided proof of principle that intrastriatal transplants of fetal dopaminergic neurons can induce substantial and long-lasting functional benefits in patients with Parkinson's disease. However, in two recent NIH-sponsored double-blind trials, functional improvements were only marginal and the primary endpoints were not met. Severe off-phase dyskinesias were observed in a significant proportion of the transplanted patients, raising doubts about the viability of the cell-transplantation approach. Here, we discuss the problems raised by the NIH-sponsored trials and point to several shortcomings that might explain the overall poor outcome, and we identify several crucial issues that remain to be resolved to develop cell replacement into an effective and safe therapy.