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Cholera is highly endemic in many sub-Saharan African countries. The bacterium <i>Vibrio cholerae</i> is responsible for this severe dehydrating diarrheal disease that accounts for over 100,000 deaths each year globally. In recent years, the pathogen has been found to invade intestinal layers and translocate into the bloodstream of humans. The non-toxigenic strains of <i>V</i>. <i>cholerae</i> (non-O1/O139), also known as NOVC, which do not cause epidemic or pandemic cases of cholera, are the major culprits of <i>V</i>. <i>cholerae</i> bacteremia. In non-cholera-endemic regions, clinical reports on NOVC infection have been noted over the past few decades, particularly in Europe and America. Although low–middle-income countries are most susceptible to cholera infections because of challenges with access to clean water and inappropriate sanitation issues, just a few cases of <i>V</i>. <i>cholerae</i> bloodstream infections have been reported. The lack of evidence-based research and surveillance of <i>V. cholerae</i> bacteremia in Africa may have significant clinical implications. This commentary summarizes the existing knowledge on the host risk factors, pathogenesis, and diagnostics of NOVC bacteremia.