The article reviews the molecular mechanisms of Escherichia coli pathogenicity, focusing on the recent advances in understanding the different pathogenic mechanisms used by various E. coli pathovars to cause disease in humans. E. coli, a diverse organism, can become a highly adapted pathogen by acquiring mobile genetic elements. Eight well-characterized pathovars have been identified, each using a large arsenal of virulence factors to subvert host cellular functions. The review highlights the importance of adhesion, hijacking host cell signaling pathways, and evasion of immune responses in the pathogenicity of E. coli. It also discusses the evolution of pathogenicity through horizontal gene transfer and the acquisition of virulence genes, particularly in pathogenicity islands (PAIs). The article provides detailed insights into the mechanisms of specific pathovars, such as enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), diffusely adherent E. coli (DAEC), uropathogenic E. coli (UPEC), and neonatal meningitis E. coli (NMEC). Each pathovar has unique mechanisms for colonization, invasion, and disease induction, contributing to the global burden of E. coli-related diseases. The review emphasizes the complex interactions between E. coli and host cells, providing a comprehensive overview of the molecular mechanisms underlying E. coli pathogenicity.The article reviews the molecular mechanisms of Escherichia coli pathogenicity, focusing on the recent advances in understanding the different pathogenic mechanisms used by various E. coli pathovars to cause disease in humans. E. coli, a diverse organism, can become a highly adapted pathogen by acquiring mobile genetic elements. Eight well-characterized pathovars have been identified, each using a large arsenal of virulence factors to subvert host cellular functions. The review highlights the importance of adhesion, hijacking host cell signaling pathways, and evasion of immune responses in the pathogenicity of E. coli. It also discusses the evolution of pathogenicity through horizontal gene transfer and the acquisition of virulence genes, particularly in pathogenicity islands (PAIs). The article provides detailed insights into the mechanisms of specific pathovars, such as enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), diffusely adherent E. coli (DAEC), uropathogenic E. coli (UPEC), and neonatal meningitis E. coli (NMEC). Each pathovar has unique mechanisms for colonization, invasion, and disease induction, contributing to the global burden of E. coli-related diseases. The review emphasizes the complex interactions between E. coli and host cells, providing a comprehensive overview of the molecular mechanisms underlying E. coli pathogenicity.