Rifaximin, a virtually nonabsorbed (<0.4%) rifamycin drug, has in vitro activity against aerobic and anaerobic gram-positive and gram-negative microorganisms. Because rifaximin is nonabsorbed, systemic adverse effects are unusual, and after 3 days of therapy, the fecal level of the drug reaches 8000 microg/g. Moreover, the important selection of resistant mutants by the related drug, rifampin, has not yet been observed for rifaximin. Rifaximin has been demonstrated to reduce the duration of traveler's diarrhea secondary to noninvasive bacterial pathogens and recently has been shown to reduce the occurrence of the disease when used for chemoprophylaxis. Preliminary studies have demonstrated its potential for the treatment of other gastrointestinal disorders, such as hepatic encephalopathy. Additional studies should be performed to further define the role of rifaximin in the treatment of gastrointestinal diseases in adults and children.