In addition to the well-established and extensively studied categories of pathogenic E. coli, there are other groups of E. coli associated with diarrheal and/or inflammatory bowel diseases that have not been thoroughly characterized or which are considered newly emergent pathogens. This chapter focuses on three representatives of these groups of pathogenic E. coli and the current progress understanding their role in pathogenesis. Diffusely adherent E. coli (DAEC) are a collection of isolates that colonize the small bowel, considered potentially diarrheagenic, and that can cause childhood diarrhea. Adherent and invasive E. coli (AIEC) are a group of mucosa-associated bacteria with invasive properties in Crohn’s disease patients and can survive and replicate extensively in macrophages. Finally, E. coli O104:H4, a hybrid Shiga toxin-producing enteroaggregative E. coli, which caused a large outbreak in Europe in 2011, displays a unique combination of virulence traits resulting in the development of hemolytic uremic syndrome in an unusually large proportion of infected patients. This chapter summarizes recent progress in understanding the pathogenesis and the clinical outcome of these types of E. coli infections.