Rifaximin is a rifamycin analogue with a broad spectrum of activity similar to that of rifampin; however, because it is poorly absorbed in the gastrointestinal tract, the focus of its development has been on intestinal infections and diseases. This agent has proven to be as effective as ciprofloxacin in treating travelers' diarrhea due to Escherichia coli, although it is ineffective in treating infections due to Campylobacter jejuni. Other potential uses for rifaximin in gastroenterologic disorders include treatment of hepatic encephalopathy, intestinal gas and gas-related symptoms, diverticular disease, intestinal bacterial overgrowth, pouchitis, ulcerative colitis, and active Crohn's disease. This article highlights several studies demonstrating the efficacy of rifaximin in treating travelers' diarrhea as well as other gastrointestinal diseases and discusses the drug's pharmacokinetics, indications, contraindications, warnings, precautions, adverse reactions, and dosing.