One-anastomosis gastric bypass is an alternative to the “gold-standard” Roux-en-Y gastric bypass. This technique appears to be safe and efficient, but controversy remains regarding the long-term theoretical risk of subsequent biliary reflux and its possible complications, such as cancer. The aim of the present narrative review was to summarize some of the current thoughts on biliary reflux. Research has established that exposure to chronic bile reflux in humans and rats (outside the “bariatric surgery” box) induce esophageal intestinal metaplasia and esophageal adenocarcinoma. Although one-anastomosis gastric bypass can theoretically induce chronic biliary reflux, the incidence of biliary reflux and risk of cancer have not been prospectively evaluated. Clarification of this controversial issue is urgently needed.