Vibrio cholerae a global health concern, causing intestinal diarrhea in human, mostly found in aquatic ecosystem, now expand its habitats to various ecological setting with diverse host range. It harbours two chromosomes with unique features, making it an emerging model bacterium for studying microbial genetics, functions, and evolution, specifically for multi-chromosomal bacteria. V. cholerae served as a model in host–pathogen interaction studies, which include oral infection models in Drosophila melanogaster and in quorum sensing as well as in biofilm research. This bacterium has been used to model climate-sensitive infectious diseases and leveraged as a key organism for studying heterotrophic bacteria in natural ecosystems. Despite current developments in the field of V. cholerae research, additional exploration is essential before claiming this bacterium as a great model microbe.