Radiofrequency ablation (RFA) is a well-established treatment for several benign, premalignant, and malignant disorders. Although the role of RFA has been clearly defined, new indications for luminal and extraluminal applications of endoscopic RFA-directed therapies have emerged. RFA has recently produced promising results in patients with a variety of gastrointestinal and hepatopancreatobiliary pathologies. For example, endoscopic RFA has been used to treat patients with gastric antral vascular ectasia, chronic radiation proctitis, malignant biliary strictures, and ampullary adenomas with intraductal extension. Furthermore, endoscopic ultrasound-guided RFA appears to be an effective, minimally invasive treatment for ablation of solid and cystic lesions—particularly in the pancreas. We review the newer indications for RFA and discuss potential limitations of endoscopic RFA.