Cholera is an acute diarrheal illness burdening several developing countries caused by toxigenic Vibrio cholerae, where endemics maintain a seasonal pattern and occur more than once a year. Cholera is endemic in certain regions of Africa and South America, and southern Asia, where outbreaks are associated with poor hygiene and sanitary conditions. Every year, 3–5 million cases of cholera are diagnosed, and it causes more than 100,000 deaths worldwide. Cholera toxin is secreted by the V. cholerae bacteria and causes extreme secretory diarrhea, most commonly in poor hygiene environment. Watery diarrhea, vomiting, and abdominal cramps characterize the illness and approximately 5–10% of patients die of severe fluid loss if left untreated. The structure and function of the cholera toxin, its subunits, receptor, and impact on hyperactivation of cyclic adenosine monophosphate (cAMP) were sufficiently described in the 1970s. These findings fit with epidemiologic observations, which determined that the cholera toxin must first enter intestinal cells by binding to monosialoganglioside (GM1) on the host’s epithelial surface. The correlation between increase risk of V. cholerae infection and individuals with a particular ABO blood group type is unclear because of the scarce information and few studies conducted. Thus, this study reviews published research articles to better understanding the association between the blood group O and susceptibility to developing severe cholera symptoms. Several large studies have recorded an association between ABO blood groups and different infectious agents). Anthropological surveys suggest that the racial and geographic distribution of human blood types reflects tendencies towards specific erythrocyte types susceptible to infectious disease, such as cholera and malaria. Experimentally, the V. cholerae toxin has been extensively used as an experimental adjuvant, and its association with ABO groups is of practical importance for the development of an oral cholera vaccination. The results of previous studies provided strong evidence that individuals with blood type O are more vulnerable than other persons to severe cholera symptoms, even though the biologic basis for this association remains unknown.