Stem cell therapy is considered a promising strategy aiming at neuronal and glial cell replacement or neuroprotection in neurological diseases affecting the brain and spinal cord. Multiple Sclerosis (MS), characterized by inflammation-induced destruction of the myelin sheath surrounding axons leading to conduction deficits and variability of clinical signs, is not an exception. MS is considered an autoimmune disease and, in the last few years, an intense immunodepletion followed by autologous hematopoietic-stem-cell transplant (HSCT) is being assessed as potential therapeutical strategy for severe patients unresponsive to the immunomodulatory and immunosuppressive treatment. Partially supported by evidence in animal models and by anecdotal reports on the beneficial effects on MS patients with concomitant malignant diseases, HSCT programs for MS have been initiated worldwide and follow-up data are accumulating. A Consensus Meeting has been held in Milano (1998) providing a document that defined criteria for patient selection, transplantation procedures, and outcome evaluations. Nowadays the high number of patients already treated allows us to draw initial conclusions related to clinical efficacy. After careful monitoring of the available data and improvement of the procedure, safety seems not to be anymore an issue. Ethics of HSCT deserve, on the contrary, a profound evaluation: the procedure is a multistep process with manifold options, each step with different ethical implications. Even more difficult appears the definition of the MS patient selection criteria for HSCT. The informed consensus needs to be exhaustive for the full comprehension of a complex procedure. In conclusion, although HCST is today an established therapeutical option for MS patients, safety and ethical issues need to be further clarified.