In Mexico, diarrhea diseases are the second leading cause of death in children ≤ 5 years old. Studies regarding enteropathogens associated with severe acute diarrhea, requiring hospitalization, have revealed diarrheagenic Escherichia coli pathotypes (DEC) as the second most prevalent group, only after rotavirus, in children of this age. DEC epidemiology has changed throughout the years, until the mid ‘90s enterotoxigenic E. coli and typical enteropathogenic E. coli (tEPEC) strains were more often isolated from children aged ≤ 5 years, nowadays is enteroaggregative E. coli (EAEC) followed by atypical EPEC. Other DEC identified these days include, ETEC, non-O157:H7 Shiga-toxin producing E. coli (STEC), tEPEC and enteroinvasive E. coli (EIEC). DEC strains have been isolated from local food samples in enough quantities to cause disease. Non-O157:H7 STEC strains have been identified from stool samples from asymptomatic subjects, diarrhea cases and a variety of food items, but O157:H7 serotype prevalence is extremely low. Mexican children and adult serum have shown, cross reactivity against O157:H7, other E. coli serogroups (O7, O116), enteric bacteria and O157:H7 bactericidal activity. Most DECs strains isolated from diarrhea patients and food samples were resistant to TMP-SMX and ampicillin; almost all strains were ciprofloxacin and cefotaxime sensitive. A new E. coli serogroup (64474) sharing only a common O antigen with S. boydii 16, has been identified. Further, substantial reductions in diarrhea related deaths, complications and morbidity due to acute diarrhea episodes, will require sanitation improvement, identification of enteropathogens and development of both new drugs to treat pediatric diarrhea and vaccines against DEC.