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For the last two decades, upper gastrointestinal endoscopy has been a diagnostic procedure carried out for investigations of malabsorption or gastrointestinal bleeding. However, in the last 10 years, rapid advances have been made in therapeutic upper gastrointestinal endoscopy for a range of gastrointestinal conditions, for the treatment of benign and early neoplastic lesions, management of advanced cancer and expanding indications of metabolic endoscopy and gastro-oesophageal reflux disease. The repertoire of therapeutic procedures in the upper gastrointestinal tract now include resection and ablation of early neoplastic lesions associated with Barrett’s oesophagus, endoscopic submucosal dissection for early squamous neoplasia of the oesophagus and early gastric cancer, resection of duodenal lesions, resection of subepithelial lesions, management of benign and malignant stenosis, third space endoscopic procedures for achalasia (per oral endoscopic myotomy, POEM) and for gastroparesis (G-POEM), treatment of Zenker’s diverticulum (Z-POEM), endoscopic sutured gastroplasty and duodenal ablation procedures for treatment of obesity and diabetes, and endoscopic vacuum therapy for management of leaks, defects and fistulas.In the first of a two-part series on therapeutic upper gastrointestinal endoscopy, we aim to describe some of these innovations with indications, a brief description of the procedure and the evidence base for their use in gastrointestinal endoscopy.