Recent evidence supports the existence of adult mammalian stem cell subpopulations, particularly within the bone marrow, that may be able to "transdifferentiate" across tissue lineage boundaries, thus offering an accessible source for therapeutic applications even for neural tissue repair. However, the difficulties in reproducing some experimental data, the rarity of the transdifferentiation events and observations that cell fusion may be an alternative explanation argue against the idea of stem cell plasticity. Investigations going beyond descriptive experiments and more mechanicistic approaches may provide a more solid foundation to adult stem cell therapeutic potential.