Oral rifaximin, a semisynthetic rifamycin derivative, is an effective and well tolerated antibacterial for the management of adults with non-invasive traveller's diarrhoea. Rifaximin was significantly more effective than placebo and no less effective than ciprofloxacin in reducing the duration of diarrhoea after treatment initiation for illness contracted during travel to diverse geographic locations. While rifaximin is effective in patients with Escherichia coli-predominant traveller's diarrhoea, it appears ineffective in patients infected with inflammatory or invasive enteropathogens. Rifaximin has a broad spectrum of antibacterial activity in vitro and undergoes negligible systemic absorption (<0.4%). In contrast to systemically absorbed antibacterials, such as the fluoroquinolones and macrolides, the acquisition of resistance to rifaximin would have limited consequences for global public health, as rifaximin has no role in the management of systemic infections. Rifaximin shows promise as chemoprophylaxis against traveller's diarrhoea and is a valuable new option for the management of traveller's diarrhoea caused by non-invasive bacterial strains.