Amebic liver abscess should be suspected in travelers returning from endemic areas or in immunocompromised patients who present with fever, right upper quadrant pain, hepatomegaly, and a liver lesion on an imaging study. Rapid initiation of therapy without serologic confirmation of infection, if necessary, is important to minimize complications. Metronidazole is given orally or intravenously for 14 days. The drug is generally well tolerated and leads to resolution of symptoms in most patients within 2 to 3 days. It is effective against luminal cysts in only 50% of patients and, therefore, must be followed by a course of treatment with paromomycin (Humatin; Parke-Davis, Morris Plains, NJ) or another luminal antiamebic agent to eradicate the parasite. Image-guided drainage of an amebic liver abscess is indicated in patients who do not respond to antimicrobial therapy or who are at risk of abscess rupture. Surgery is reserved for patients with a ruptured abscess. Although medical therapy is generally successful in the treatment of infection caused by Entamoeba histolytica, the development of potent vaccines will be needed for worldwide eradication of disease attributable to E. histolytica.