Simple SummaryThis revision is about the problem of Escherichia coli as a commensal and pathogenic bacterium among food-producing animals and health implications. Escherichia coli may play an important ecological role and can be used as a bioindicator of antimicrobial resistance. All animal species used for food production, as well as humans, carry E. coli in their intestinal tract; plus, the genetic flexibility and adaptability of this bacteria to constantly changing environments allows it to acquire a great number of antimicrobial resistance mechanisms. The majority of E. coli strains are commensals inhabiting the intestinal tract of humans and warm-blooded animals and rarely causes diseases. However, E. coli also remains as one of the most frequent causes of several common bacterial infections in humans and animals. All over the word, antibiotic resistance is commonly detected among commensal bacteria from food-producing animals, raising important questions on the potential impact of antibiotic use in animals and the possible transmission of these resistant bacteria to humans through the food chain. The use, in food-producing animals, of antibiotics that are critically important in human medicine has been implicated in the emergence of new forms of resistant bacteria, including new strains of multidrug-resistant foodborne bacteria, such as extended spectrum β-lactamase (ESBL)-producing E. coli.Escherichia coli are facultative, anaerobic Gram-negative rods with many facets. Within resistant bacterial populations, they play an important ecological role and can be used as a bioindicator of antimicrobial resistance. All animal species used for food production, as well as humans, carry E. coli in their intestinal tracts; plus, the genetic flexibility and adaptability of this bacteria to constantly changing environments allows it to acquire a great number of antimicrobial resistance mechanisms. Thus, the prevalence of antimicrobial resistance in these commensal bacteria (or others, such as enterococci) can be a good indicator for the selective pressure caused by the use of antimicrobial agents, providing an early warning of the emergence of antimicrobial resistance in pathogens. As many as 90% of E. coli strains are commensals inhabiting the intestinal tracts of humans and warm-blooded animals. As a commensal, it lives in a mutually beneficial association with its hosts and rarely causes diseases. However, E. coli also remains as one of the most frequent causes of several common bacterial infections in humans and animals. In humans, it is the prominent cause of enteritis, community- and hospital-acquired urinary tract infection (UTI), septicemia, postsurgical peritonitis, and other clinical infections, such as neonatal meningitis, while, in farm animals, it is more prominently associated with diarrhea. On a global scale, E. coli can be considered the most important human pathogen, causing severe infection along with other major bacterial foodborne agents, such as Salmonella spp. and Campylobacter. Thus, the importance of resistance in E. coli, typically considered a benign commensal, should not be underestimated.