Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in developing countries and is regularly imported into developed countries as a major cause of traveler's diarrhea. ETEC is usually self-limiting and not necessarily treated with antimicrobials, although antimicrobial treatment is recommended in malnourished children, severe cases, and traveler's diarrhea. However, resistant strains to representative therapeutic agents such as ciprofloxacin and azithromycin have been reported in recent years, and multidrug-resistant ETEC has also emerged. This review discusses the recent antimicrobial resistance surveillance in ETEC and the mechanisms of resistance to major antimicrobials.