Rifaximin is a poorly water-soluble and minimally absorbed (<0.4%) rifamycin with in vitro activity against enteric Gram-negative bacteria including enteric pathogens. Fecal levels of the drug after 3 days' oral therapy exceed 8000 microg/g. Rifaximin is effective in the treatment and prevention of travelers' diarrhea due to Escherichia coli-predominant bacterial pathogens. It shows lower activity against dysenteric forms of bacterial diarrhea. The drug may be useful in other enteric infectious diseases, including Clostridium difficile colitis, pediatric bacterial diarrhea and Helicobacter pylori gastritis and chronic gastrointestinal disorders including hepatic encephalopathy, small bowel bacterial overgrowth, inflammatory-bowel disease, irritable-bowel syndrome and pouchitis. Importantly, rifaximin does not appear to lead to bacterial resistance. Rifaximin has an excellent safety profile and adverse drug reactions have been comparable to those associated with the placebo control agent.