Zinc (Zn) concentration in wheat grains is generally low, with an average value of around 28–30 mg/kg. Therefore, increasing wheat grain Zn concentration for better human health is the focus of HarvestPlus global initiatives. Source–sink interactions have been intensively studied for decades to enhance crop yield potential, but less on grain nutritional quality. This review applies concepts of source, sink, and their interactions to the study of wheat grain Zn nutrition and biofortification. Increasing Zn sources to wheat (via soil and foliar application) could directly enlarge available Zn in vegetative tissues and grain Zn sink. Rational nitrogen (N) supply increases grain Zn accumulation (N‐Zn synergism), but phosphorus (P) input generally decreases (P‐Zn antagonism), and the potassium (K) effect is unclear. Conventional and genetic breeding have potential to stimulate Zn flow from source to sink (uptake from soil, root‐to‐shoot translocation, and remobilization). However, a rational manipulation to establish a well‐coordinated source–sink relationship is required to finally realize the grain Zn target (40–50 mg/kg) and increase on‐farm crop yield. Future studies should focus more on fertilization modes adopted by farmers (uses of compound, slow/controlled release, and organic and microbial fertilizers) and develop integrated agronomic and genetic strategies for Zn biofortification. A highly systematic and mechanistic model includes (a) migration paths of Zn (particularly from leaves to different grain parts) using isotopic labeling methods, (b) cross‐talks between Zn and carbon, N, P, K, or other divalent cations, (c) inherent physiological and biochemical processes of enzymes and signaling phytohormones, and (d) complex genetic systems governing Zn homeostasis and their relationships with other nutrients, signaling molecules, and increase or dilution/penalty of yield under different environmental conditions (soil, water, and future climatic changes) and managements (breeding and fertilization). These aspects require further elucidation to fully unravel the “black box” of Zn flow from source to sink.
