Urinary tract infections (UTIs) are among the most common infections encountered worldwide in clinical practice. Escherichia coli is by far the most frequent cause of infections responsible for nearly 80–90% of the infections. The strains of E. coli causing UTI are termed as uropathogenic E. coli. They vary from commensal strains as they have acquired virulence and resistant determinants through plasmids, bacteriophages, pathogenicity islands or DNA horizontal transfer of transposons which permits them to victoriously colonize the urinary tract and cause a broader spectrum of disease. For the fact, UPEC strains possess an abundance of both structural (as fimbriae, pili, flagella, capsule, lipopolysaccharide) and secreted (toxins, iron-acquisition systems, enzymes) virulence factors that play a crucial role in the pathogenesis. The pathogenesis of UPEC involves adherence, colonization, evading host defenses and damage to host tissue to achieve virulence. UTI is often treated empirically by broad-spectrum antibiotics in the absence of culture and susceptibility results. This over-use of antibiotics has resulted in the development of antibiotic resistance worldwide. Having a detailed understanding of the bacterium and its virulence factors can help us in developing new treatment options in presence of global antimicrobial resistance.