After a brief historical background on pancreas transplantation in the treatment of diabetes mellitus, this review deals with the major surgical, pharmacological and functional aspects of this approach. In the Authors' opinion pancreas transplantation should be proposed only when the end-stage renal failure (ESRF), due to diabetic nephropathy, needs kidney transplantation. By using injection of polymers (mainly neoprene) into the pancreatic ducts, or urinary diversion of pancreatic juice and appropriate immunosuppressive therapy (cyclosporin, corticosteroids and azathioprine), dramatic advantages have been achieved in the last years, so that a satisfactory segmental or total pancreas graft survival on one hand, and the early graft rejection recognition on the other have been presently obtained. A prompt and good functional activity of pancreas graft has also been demonstrated by the Authors in successfully transplanted patients. As far as chronic diabetic complications are concerned, no conclusive results have been reported up to now; it is noteworthy, however, that pancreas transplantation may preserve the transplanted kidney from a relapse of diabetic nephropathy. The combined pancreas-kidney transplantation may actually be considered as a correct solution to the problem of diabetic patients with ESRF. Moreover, careful selection of patients, appropriate surgical technique and experienced immunosuppressive treatment are the major prerequisites to achieve a satisfactory improvement of diabetic status in addition to that of renal failure.