We describe the evaluation and initial management of key symptoms prevalent in esophageal disease. Heartburn and regurgitation are 2 symptoms of gastroesophageal reflux disease (GERD), the most common outpatient gastrointestinal tract disease. The initial diagnostic and therapeutic step in management of these hallmark GERD symptoms is an empirical trial of acid suppression therapy, as a response to this is sufficient to diagnose GERD. Patients with symptoms refractory to empirical therapy and those who endorse accompanying alarm symptoms such as dysphagia, melena, anemia, or weight loss need an upper endoscopy to rule out more serious etiologies such as esophageal or gastric carcinoma. Dysphagia can be categorized as oropharyngeal or esophageal in nature, based on patient localization of symptoms. Oropharyngeal dysphagia can be caused by dental, neuromuscular, and structural etiologies. Although it is important to clarify whether esophageal dysphagia is solid or mixed and intermittent or progressive, more cases warrant further investigation with upper endoscopy, especially if alarm symptoms are present. Odynophagia, the etiology of which can be elicited by a thorough clinical history, can be caused by caustic ingestion, pill esophagitis, and infectious esophagitis. Although verifying the etiology of globus and hiccups can be challenging, diagnostic tools such nasal endoscopy, upper endoscopy, and computerized tomography scans of the thorax can rule out the most serious causes. If initial medical therapy of symptomatic esophageal disease fails, a multidisciplinary team of dieticians, surgeons, and gastroenterologists can guide further evaluation and treatment.