Zinc (Zn) is an essential micronutrient to plants as it is involved in different processes, influencing growth, development, and yield. Consequently, Zn deficiency in agricultural soils restricts crop yield, in addition to affecting the nutritional quality of plant-based foods. Zn deficiency also causes serious human health problems. Therefore, elucidating the chemical reactions of Zn in the soil as well as the uptake and transport by the plants is necessary. Different approaches to mitigate Zn deficiency effects can be outlined. Application of fertilizers, biostimulators, and nanoparticles and the development of new genotypes that improved Zn use efficiency are some important approach to deal with Zn deficiency. The creation of new cultivars can be achieved using conventional or molecular breeding techniques. In conventional breeding, the available genetic diversity is explored, using hybridization and artificial selection tools, while in molecular breeding, different tools are applied to identify candidate genes, such as molecular markers, genetic mapping, and gene expression analyses. The identified genes can be manipulated through transgenics and genome editing. Considering the impact of Zn deficiency on the productivity of cultivated plants and on human health, this chapter aims to provide information about genes involved in Zn uptake, breeding strategies, and modern tools applied to fight against Zn deficiency.