With the advent of transplantation and the acquired immunodeficiency syndrome (AIDS), esophageal infections are now a common medical problem. The most common infections involving immunocompromised nonhuman immunodeficiency virus (HIV)-infected patients include viral disease (herpes simplex virus and cytomegalovirus) and Candida. In HIV-infected patients, Candida esophagitis is by far the most common infection; viral disease is seen less frequently. In contrast to other immunocompromised patients, these patients may have esophageal disease from a variety of other fungi and viruses. Immunocompromised patients in whom esophageal symptoms develop after transplantation usually undergo endoscopy for diagnosis because of the possibility that alterations in immunosuppressive agents will be required if an opportunistic infection is causative. In contrast, HIV-infected patients with new-onset esophageal symptoms are usually treated empirically with oral systemic antifungal therapy given the prevalence of Candida esophagitis. Barium esophagography may, however, be worthwhile, depending on the clinical setting, such as the possibility of a reflux-induced stricture. In HIV-infected patients, radiography is less often utilized in the setting of a low CD4 lymphocyte count given the likelihood of an opportunistic infection that requires endoscopic biopsy for a definitive diagnosis. Oral systemic antifungal therapy with either ketoconazole or fluconazole is very effective for the treatment of Candida esophagitis, and these agents have also shown efficacy in the prophylaxis of fungal infections following transplantation, as well as in patients with AIDS following oropharyngeal and esophageal candidiasis. Antiviral therapy with acyclovir for herpes simplex virus and ganciclovir and foscarnet for cytomegalovirus are effective. The efficacy rate for these antiviral agents appears similar in all immunocompromised patients. These agents have also been utilized prophylactically following transplantation. In summary, a variety of infections may involve the esophagus in immunocompromised patients. The diagnostic strategies utilized in these patients are similar; endoscopy and biopsy are the most cost-effective strategy given the need for mucosal biopsy for a definitive diagnosis. Importantly, efficacious therapy is available to treat these disorders. Nevertheless, in patients with AIDS, identification of an opportunistic esophageal disease portends a poor prognosis.