Vibrio cholerae causes the diarrheal disease cholera primarily because it expresses a colonization factor (toxin-coregulated pilus; TCP) and a potent toxin (cholera toxin; CT) within the human intestine. While the true environmental signals that induce CT and TCP expression within the intestine remain unknown, much progress has been made identifying the regulatory factors that modulate their expression. Transcriptional regulation of the genes encoding TCP and CT involves a cascade consisting of a number of regulatory factors located on recently acquired mobile genetic elements as well as others residing within the ancestral Vibrio genome. In vivo studies have revealed interesting differences between the regulation of TCP and CT expression in the laboratory and within the intestine.