Diarrhea continues to be the leading health problem among international travelers to developing tropical and semi-tropical regions. Despite more than 50 years of research providing information about the etiology and pathogenesis of the disease, the rate of illness and consequences remain unchanged. An estimated 40% of travelers to developing nations will become ill with diarrhea. Although travelers' diarrhea is considered a self-limited disease, novel and effective approaches to disease prevention and treatment have been realized in recent years. Also, recent evidence has identified a potential for long-term complications of the illness, including postinfectious irritable bowel syndrome. With the advent of poorly absorbed (<0.4%) rifaximin, a treatment option for the common watery diarrhea syndrome equivalent to previously used absorbed antibacterial drugs has emerged. Rifaximin with an excellent safety profile and limited potential to induce coliform resistance, prevents most of the diarrhea that would otherwise occur. With further studies in different settings, new consideration should be given to the routine use of chemoprophylaxis for travelers to high-risk countries. Antibacterial drugs will continue to be the optimal treatment for travelers' diarrhea subjects for the most part caused by bacterial enteropathogens and shorten the duration of diarrhea by 1-2 days compared with no active drug treatment.