Esophageal disease is a common complication and cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Opportunistic esophageal diseases may occur in patients with long-standing infection or may be the initial manifestation of HIV disease. Although a variety of both opportunistic and nonopportunistic disorders result in esophageal disease in this population, candidal esophagitis is the most common cause of symptomatic disease. Ulcerative esophagitis resulting from cytomegalovirus and idiopathic esophageal ulceration constitute the next most important etiologies. In contrast to other immunocompromised hosts, herpes simplex virus esophagitis appears to be relatively uncommon. Multiple simultaneously discovered esophageal disorders have been documented in up to 50% of patients. Opportunistic neoplasms are an infrequent cause of symptomatic disease. Candidal esophagitis may present with either dysphagia or odynophagia, and oropharyngeal candidiasis is usually present at the time of diagnosis. In contrast, ulcerative esophagitis is usually first manifested by moderate to severe odynophagia. Barium esophagography and upper endoscopy are the most commonly employed diagnostic modalities for the evaluation of the symptomatic patient. Although barium esophagography may identify specific abnormalities, this procedure appears to be relatively insensitive for the detection of mild candidal disease as well as nondiagnostic for ulcerative lesions when compared with endoscopy. In the HIV-infected patient with new-onset esophageal symptoms, an empiric trial of a systemically acting oral antifungal agent should probably be the initial management strategy. If the patient does not respond to standard therapy within 1 to 2 weeks, an endoscopic evaluation appears to be the most cost-effective diagnostic test given the diversity of potential disorders, the possibility of one or more co-pathogens or diseases, the potential for an immediate diagnosis, and the availability of mucosal biopsy to make a definite diagnosis of ulcerative or mass lesions. Given the presently available therapy for these diverse processes, establishing a definitive diagnosis in the symptomatic patient not responsive to empiric antifungal therapy is warranted.