Beta-cell replacement therapy, a whole pancreas as well as pancreatic islets transplantation, is nowadays the only one that restores the physiological endogenous insulin secretion in patients with type 1 diabetes mellitus. Beside unquestionable benefits both methods create a risk of complications, requiring future studies in order to be eliminated, and considering an increasing amount of transplantation procedures an insufficient number of organ donors may become a real problem. The future of diabetes therapy depends on the progress in new immunosuppressive and/or immunomodulatory therapy, alternative sources of pancreatic islets and transplantation strategies development.