Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux 
in the distal oesophagus, and this may cause the development of reflux 
esophagitis and Barrett's oesophagus (BE). The natural histological course of 
untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and 
High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy 
transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE 
diagnostics involves high-resolution white-light endoscopy, followed by uniform 
endoscopy findings description (Prague classification) with biopsy performance 
according to Seattle protocol. The medical treatment of GERD and BE includes the 
use of proton pump inhibitors (PPIs) regarding symptoms control. It is 
noteworthy that long-term use of PPIs increases gastrin level, which can 
contribute to transfer from BE to EAC, as a result of its effects on the 
proliferation of BE epithelium. Endoscopy treatment includes a wide range of 
resection and ablative techniques, such as radio-frequency ablation (RFA), often 
concomitantly used in everyday endoscopy practice (multimodal therapy). RFA 
promotes mucosal necrosis of treated oesophagal region via high-frequency 
energy. Laparoscopic surgery, partial or total fundoplication, is reserved for 
PPIs and endoscopy indolent patients or in those with progressive disease. This 
review aims to explain distinct effects of PPIs and RFA modalities, illuminate 
certain aspects of molecular mechanisms involved, as well as the effects of 
their concomitant use regarding the treatment of BE and prevention of its 
transfer to EAC.