Humans have an important association with their intestinal microbial flora. The microbial flora helps to shape the mammalian innate immune system, absorbs nutrients, and plays an intricate role on intestinal development. Microbes and mammals communicate with each other through an array of hormone and hormonelike chemical compounds. These "signals," however, are hijacked by bacterial pathogens, such as enterohemorrhagic Eschrichia coli (EHEC), to activate its virulence genes, colonize the host, and start the disease process. This review explores the cell-to-cell signaling events in the gastrointestinal tract that lead EHEC to regulate its virulence genes in a coordinate manner.