Abstract: Diarrhea caused by Vibrio cholerae non-O1/O139 occurs frequently in many developing countries, several serogroups are involved the epidemic. In some places, the incidence of diarrhea caused by V. cholerae non-O1/O139 was even higher than that of O1 and O139 serogroups. It is believed that several virulence factors play the important roles in the pathogenicity of V. cholerae non-O1/O139, including enterotoxin, protease, hemolysin and the type three secretion system (TTSS), et al, but its pathogenic mechanism is very complicated and still not fully understood. Meanwhile, drug resistant and even multidrug resistant strains have emerged. This paper summarizes the research progress in the epidemic of diarrhea caused by V. cholerae non-O1/O139, its virulence factors and drug resistance.