Zinc (Zn) is an important micronutrient in the human body, and health complications associated with insufficient dietary intake of Zn can be overcome by increasing the bioavailable concentrations in edible parts of crops (biofortification). Wheat (Triticum aestivum L) is the most consumed cereal crop in the world; therefore, it is an excellent target for Zn biofortification programs. Knowledge of the physiological and molecular processes that regulate Zn concentration in the wheat grain is restricted, inhibiting the success of genetic Zn biofortification programs. This review helps break this nexus by advancing understanding of those processes, including speciation regulated uptake, root to shoot transport, remobilisation, grain loading and distribution of Zn in wheat grain. Furthermore, new insights to genetic Zn biofortification of wheat are discussed, and where data are limited, we draw upon information for other cereals and Fe distribution. We identify the loading and distribution of Zn in grain as major bottlenecks for biofortification, recognising anatomical barriers in the vascular region at the base of the grain, and physiological and molecular restrictions localised in the crease region as major limitations. Movement of Zn from the endosperm cavity into the modified aleurone, aleurone and then to the endosperm is mainly regulated by ZIP and YSL transporters. Zn complexation with phytic acid in the aleurone limits Zn mobility into the endosperm. These insights, together with synchrotron‐X‐ray‐fluorescence microscopy, support the hypothesis that a focus on the mechanisms of Zn loading into the grain will provide new opportunities for Zn biofortification of wheat.