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Helicobacter pylori (H. pylori) are resistant to hostile gastric environments and antibiotic therapy, reflecting the possibility that they are protected by an ecological niche, such as inside the vacuoles of human epithelial and immune cells. Candida yeast may also provide such an alternative niche, as fluorescently labeled H. pylori were observed as fast-moving and viable bacterium-like bodies inside the vacuoles of gastric, oral, vaginal and foodborne Candida yeasts. In addition, H. pylori-specific genes and proteins were detected in samples extracted from these yeasts. The H. pylori present within these yeasts produce peroxiredoxin and thiol peroxidase, providing the ability to detoxify oxygen metabolites formed in immune cells. Furthermore, these bacteria produce urease and VacA, two virulence determinants of H. pylori that influence phago-lysosome fusion and bacterial survival in macrophages. Microscopic observations of H. pylori cells in new generations of yeasts along with amplification of H. pylori-specific genes from consecutive generations indicate that new yeasts can inherit the intracellular H. pylori as part of their vacuolar content. Accordingly, it is proposed that yeast vacuoles serve as a sophisticated niche that protects H. pylori against the environmental stresses and provides essential nutrients, including ergosterol, for its growth and multiplication. This intracellular establishment inside the yeast vacuole likely occurred long ago, leading to the adaptation of H. pylori to persist in phagocytic cells. The presence of these bacteria within yeasts, including foodborne yeasts, along with the vertical transmission of yeasts from mother to neonate, provide explanations for the persistence and propagation of H. pylori in the human population. This Topic Highlight reviews and discusses recent evidence regarding the evolutionary adaptation of H. pylori to thrive in host cell vacuoles.