Escherichia coli is a normal inhabitant of the enteric microflora of human and animal. Intestinal and extra-intestinal infections caused by E. coli in mammals are characterized by the presence of diversity of virulence factors. In addition it can be isolated from environment surrounding human and animal farms. E. coli is the main environmental pathogen causing clinical mastitis in dairy cattle. It causes a wide range of disease severity, from changes seen exclusively in milk to severe systemic signs. The severity of clinical mastitis has been conventionally classified into three levels: mild (grade 1), moderate (score 2), and severe (score 3). Recently, reports of cases of bovine mastitis caused by environmental agents have been on the rise, in particular in countries that have succeeded in controlling contagious microorganisms. Unlike enteric and certain extra-enteric conditions in domestic animals and humans, the impact of virulence factors on the occurrence of bovine mastitis due to E. coli, as well as the clinical severity of the cases, is not fully understood. In this regard, the present study reviewed the most relevant virulence factors of E. coli in human and animals, with emphasis in bovine mastitis.