Till this day, surgery remains the only chance of improving long-term survival in patients with periampullary and pancreatic head cancer. The procedure of choice in these cancers is pancreatoduodenectomy (PD). Associated with high morbidity, PD continues to pose a formidable challenge to pancreatic surgeons around the world. The falling mortality seen following the procedure has often been attributed to improvements in perioperative care - critical care, interventional radiology, and higher generation antibiotics. However, it would not be correct to totally ascribe these improvements only to the advancements in medical management. Developments in the understanding of the anatomical and pathophysiological factors that play a role in surgery around the pancreatoduodenal region have led to progressive modifications in the technique of pancreatoduodenectomy since it was first described in 1898. This review aims at highlighting the important milestones in the history of pancreatoduodenectomy leading to its progressive development, whilst providing a scientific basis.