Symptoms, endoscopy, and pathology are key factors in diagnosing gastroesophageal reflux disease (GERD). Endoscopy has seen relevant improvements (magnifying endoscopy, chromoendoscopy, narrow band imaging, autofluorescence, endomicroscopy) during the past years, allowing more-targeted biopsies. However, histological diagnosis of gastroesophageal reflux disease (GERD) remains difficult. Previous publications showed only a weak relationship between endoscopic and histological diagnosis. Thus, besides the classical histological parameters suggestive of GERD (length of epithelial papillae, thickness of basal cell layer), new markers such as dilatation of intercellular spaces have been introduced. Reflux lesions are rather localized, and biopsies in previous studies might not have been taken from esophageal areas with the most prominent changes. New endoscopic techniques can help to overcome this problem and offer, in addition, early detection of Barrett's esophagus and associated neoplasias in patients with chronic reflux disease. A multistep process in the histogenesis of Barrett's might explain why clearly described segments of columnar metaplasia do not show goblet cells histologically as an unequivocal sign of Barrett's metaplasia. Because early Barrett's neoplasia might be hard to detect with conventional endoscopic techniques, "blind" quadrant step biopsies are still recommended. Recent developments and improvements in endoscopic visualization might allow more-precise analysis of even very minute mucosal changes. This review discusses recent developments and findings in the field of gastrointestinal endoscopy and histology to further improve the understanding and knowledge of GERD. Gastroenterologists, surgeons, and pathologists should be aware of recent findings to ensure the best diagnostic and therapeutic approach for affected patients.