Background: Total pancreatectomy is an obligatory surgical procedure in locally advanced or centrally located pancreatic neoplasms to achieve complete tumour clearance. Owing to sound understanding of tumour biology and evolution in intervention technique and improved postoperative care, nowadays the indications of total pancreatectomy have taken a significant change. Aim: To review the indications of total pancreatectomy and its advantages and disadvantages under current perspectives. Method: Major databases, including PubMed, EMBASE, Science Citation Index Expanded, Scopus and the Cochrane Library, were searched for studies of total pancreatectomy and the results reported by various authors were summarized. Results: The indications of total pancreatectomy in subjects diagnosed with chronic pancreatitis were classified into four subgroups, including "Tumour", "Trouble", "Technical difficulties" and "Therapy-refractory pain". Today, total pancreatectomy has more specific and different indications than before. Currently, IPMN (intraductal papillary mucinous neoplasm) seems to have the most essential indication quantitatively. Morbidity and mortality related to total pancreatectomy are more profoundly decreased than before due to improvements in the operative techniques and post-operative managements. Some of the metabolic disorders are reported as major disadvantages of total pancreatectomy. Conclusion: Despite the disadvantages of total pancreatectomy, it remains an inevitable procedure for subjects with chronic pancreatitis, improvements in operative techniques and postoperative management ensuring long-term survival, a better quality of life, and diminished mortality and morbidity rates.