[Background] Total pancreatectomy (TP) has initially been reported in the 1940s for the radical treatment of chronic pancreatitis [1]. Due to the historically high surgical morbidity as well as mortality, a widespread use has not occurred within the following decades. Furthermore, the unavoidable consequence of insulin dependency has prevented wide acceptance. [Current Situation] Since the early 2000s, TP has seen a revival, not only for therapy of chronic pancreatitis but especially in pancreatic cancer (PDAC) surgery [2]. This can be attributed to a continuous improvement of surgical techniques and complication management as well as the improvements in care for exocrine and endocrine consequences of this radical operation [3, 4]. Besides standard TP, also extended approaches have been increasingly reported and TP can today be categorized in a four-tier classification, including standard TP, TP with venous resection, TP with additional organ resection and TP with arterial resection [5]. Another important aspect is the increasing use of neoadjuvant therapy for borderline resectable and locally advanced PDAC, which allows to increase the number of patients who qualify for (also extended) PDAC surgery including TP without compromising oncological results [6]. [Future Perspective] On one hand, with the upcoming aim of personalizing PDAC therapy and potential new prognostic markers, TP can be expected to be a solid and widely accepted surgical component for respectively selected patients who can benefit from this approach due to a favourable tumour biology. On the other hand, it can be expected that TP – such as other pancreatic resections – will be increasingly performed minimally-invasive and especially robotically in the future [7]. In addition, further evidence on short- and long-term outcomes will be generated to allow a better evaluation of the true value of such innovative surgical procedures. [References] 1.) Whipple AO. Radical surgery for certain cases of pancreatic fibrosis associated with calcareous deposits. Ann Surg. 1946 Dec;124(6):991-1008. 2.) Hartwig W, Gluth A, Hinz U, Bergmann F, Spronk PE, Hackert T, Werner J, Büchler MW. Total pancreatectomy for primary pancreatic neoplasms: renaissance of an unpopular operation. Ann Surg. 2015 Mar;261(3):537-46. 3.) Scholten L, Stoop TF, Del Chiaro M, Busch OR, van Eijck C, Molenaar IQ, de Vries JH, Besselink MG; Dutch Pancreatic Cancer Group. Systematic review of functional outcome and quality of life after total pancreatectomy. Br J Surg. 2019 Dec;106(13):1735-1746. 4.) Oh MY, Kim EJ, Kim H, Byun Y, Han Y, Choi YJ, Kang JS, Kwon W, Jang JY. Changes in postoperative long-term nutritional status and quality of life after total pancreatectomy. Ann Surg Treat Res. 2021 Apr;100(4):200-208. 5.) Loos M, Al-Saeedi M, Hinz U, Mehrabi A, Schneider M, Berchtold C, Müller-Stich BP, Schmidt T, Kulu Y, Hoffmann K, Strobel O, Hackert T, Büchler MW. Categorization of Differing Types of Total Pancreatectomy. JAMA Surg. 2022 Feb 1;157(2):120-128. 6.) Inoue Y, Oba A, Ono Y, Sato T, Ito H, Takahashi Y. Radical Resection for Locally Advanced Pancreatic Cancers in the Era of New Neoadjuvant Therapy-Arterial Resection, Arterial Divestment and Total Pancreatectomy. Cancers (Basel). 2021 Apr 10;13(8):1818. 7.) Kauffmann EF, Napoli N, Genovese V, Ginesini M, Gianfaldoni C, Vistoli F, Amorese G, Boggi U. Feasibility and safety of robotic-assisted total pancreatectomy: a pilot western series. Updates Surg. 2021 Jun;73(3):955-966.