Escherichia coli is the most widely studied bacterium over the world. It is well-known that E. coli is the predominant non-pathogenic microbiota of warm blood species; however, some strains have developed the ability to cause severe diseases. Taking into account the diversity in American countries, this chapter examines the complex situation of puzzling intestinal pathogenic E. coli, also called diarrheagenic, (enteropathogenic E. coli, Shiga toxin-producing E. coli, enterotoxigenic E. coli, enteroaggregative E. coli, enteroinvasive E. coli, diffusely adherent E. coli), and extra-intestinal E. coli (uropathogenic E. coli, neonatal meningitis-associated E. coli, avian pathogenic E. coli, sepsis-associated E. coli, mammary pathogenic E. coli, endometrial pathogenic E. coli, and necrotoxigenic E. coli) in animals. In addition to E. coli-associated animal diseases, the role of carriers and reservoirs is presented, including the last regional references from synanthropic and wild animals. Findings of the last 5 years are discussed and data of the eco-epidemiology of E. coli is also included. Considering the concept of One Health, which recognizes that health of humans is connected to health of animals and the environment, the strategies to diminish illness in human population cannot exclude control and vigilance of pathogenic strains in animals. However, in E. coli control, strategies distinguish between those strains that produce animal illness and those that affect humans and have an animal reservoir. The different proposed ways to E. coli control are also discussed.