Rifaximin is a derivative of rifamycin which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration; thus it is used primarily to treat local conditions within the gastrointestinal tract. In vitro data indicate rifaximin possesses good activity against species of Staphylococcus, Streptococcus and Enterococcus but lesser activity against species of Enterobacteriaceae. Bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. Results of comparative trials demonstrate that rifaximin is similar in efficacy to neomycin and lactulose in patients with hepatic encephalopathy and appears to be better tolerated. In 1 study, cyclical administration of rifaximin for 15 days per month was associated with progressive improvement over a 3-month period. In patients with infectious diarrhoea, rifaximin induces more rapid improvement in stool consistency and decreased frequency of faecal evacuations when compared with placebo, and is similar in efficacy to neomycin. Available data suggest rifaximin may be of some use in acute diverticulitis, but its use for the prevention of inflammatory complications or for control of common symptoms of diverticulosis requires further study. Preoperative treatment with rifaximin as antibacterial prophylaxis in colorectal surgery shows some potential but should be further investigated. Overall, rifaximin may be useful as an alternative therapy in hepatic encephalopathy but more data are needed to better define its clinical potential in infectious diarrhoea, diverticular disease and as antibacterial prophylaxis prior to colorectal surgery.