Infectious esophagitis is a common problem in immunocompromised patients that can result in prolonged discomfort and malnutrition. Common infectious causes of esophagitis can be confirmed by laboratory testing, but esophagoscopy is often necessary not only to visualize the esophageal mucosa but also to obtain diagnostic biopsies. Empiric, systemic antifungal or antiherpetic therapies are often prescribed prior to confirming an etiologic diagnosis in esophagitis. In some cases, however, endoscopy is needed to guide therapy. Systemic antifungal therapy is usually superior to topical therapy for Candida esophagitis, and the first choice of agent is generally fluconazole. Valacyclovir or famciclovir are the preferred first treatments for herpetic esophagitis because of their clinical efficacy and convenient dosing schedules. Thalidomide may be useful in the management of aphthous ulcerations of the mouth and esophagus in patients with HIV.