Metal acquisition and intracellular trafficking are crucial for all cells and metal ions have been recognized as virulence determinants in bacterial pathogens. Nickel is required for the pathogenicity of H. pylori. This bacterial pathogen colonizes the stomach of about half of the human population worldwide and is associated with gastric cancer that is responsible for 800,000 deaths per year. H. pylori possesses two nickel-enzymes that are essential for in vivo colonization, a [NiFe] hydrogenase and an abundant urease responsible for resistance to gastric acidity. Because of these two enzymes, survival of H. pylori relies on an important supply of nickel, implying tight control strategies to avoid its toxic accumulation or deprivation. H. pylori possesses original mechanisms for nickel uptake, distribution, storage and trafficking that will be discussed in this review. During evolution, acquisition of nickel transporters and specific nickel-binding proteins has been a decisive event to allow Helicobacter species to become able to colonize the stomach. Accordingly, many of the factors involved in these mechanisms are required for mouse colonization by H. pylori. These mechanisms are controlled at different levels including protein interaction networks, transcriptional, post-transcriptional and post-translational regulation. Bismuth is another metal used in combination with antibiotics to efficiently treat H. pylori infections. Although the precise mode of action of bismuth is unknown, many targets have been identified in H. pylori and there is growing evidence that bismuth interferes with the essential nickel pathways. Understanding the metal pathways will help improve treatments against H. pylori and other pathogens.