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Cell replacement therapy is a widely discussed novel concept of medical treatment. The increased knowledge in the stem cell field, particularly pluripotent stem cells, potentially provides powerful tools for this therapeutic concept. A large number of disease characterized by the loss of functional cells are potential candidates for cell replacement therapy and, in this regards, Parkinson's disease is of particular interest. It is one of the most prevalent neurodegenerative diseases caused by the loss of dopaminergic neurons in the Substantia nigra pars compacta. Pharmacological therapies are valuable but suffer from the progressive decline of efficacy as the disease progresses. Cell therapy application has emerged about two decades ago as a valid therapeutic alternative and recent advances in stem cell research suggest that pluripotent stem cell transplantation may be a promising approach to replace degenerated neurons in Parkinson's disease. Various sources of pluripotent stem cells (PSC) currently tested in animal models of Parkinson's disease have proven their efficacy in relieving symptoms and restoring damaged brain function. This review summarizes and discusses the important challenges that actually must be solved before the first studies of PSC transplantation can be undertaken into humans.