Escherichia coli is the most common Gram-negative bacterial pathogen, presenting both a clinical and an epidemiological challenge. In the last decade, several successful multidrug-resistant high-risk strains, such as strain E. coli ST131 have evolved, mainly due to the growing selective pressure of antimicrobial use. These strains present enhanced fitness and pathogenicity, effective transmission and colonization abilities, global distribution due to efficient dissemination, and resistance to various antimicrobial resistances. Here, we describe the emerging trends and epidemiology of resistant E. coli, including carbapenemase-producing E. coli, E. coli ST131 and colistin resistant E. coli.