Barrett’s oesophagus (BO) is a precancerous lesion associated with the development of oesophageal adenocarcinoma (OAC). Although different types of metaplasia have been described in BO, only the presence of intestinal metaplasia with goblet cells seems to be indispensable for an accurate diagnosis. Surveillance in BO is still controversial and, to date, the endoscopic screening is recommended only for patients who have at least one risk factor for OAC in addition to chronic gastroesophageal reflux disease (GERD), including being 50 years of age, male gender, Caucasian ethnicity, hiatal hernia, increased body mass index, intra-abdominal distribution of fat, nocturnal reflux symptoms, and tobacco use. Moreover, genetic factors play an important and critical role in the development of BO. In particular, genes related to inflammation, DNA repair, and xenobiotic metabolism have been investigated. To date, relatively little is known about the mechanisms that confer susceptibility to BO carcinogenesis even though several risk factors, genetic and acquired, have been identified. Since BO is a complex disease we support the use of advanced intelligent systems to integrate all the variables involved in this complex pathology and in its progression to cancer. In this review we summarise some of the most interesting controversial topics about the diagnosis, pathogenesis, management, and treatment of BO