Sulphur (S) is required in considerable amounts by all organisms, while selenium (Se) is beneficial for plants and essential for animals albeit in only small amounts. Due to their chemical similarity that is in parts also shared with molybdenum and chromium, inorganic sulphate and selenate are taken up by plants and assimilated in reduced form into organic compounds, most notably cysteine and selenocysteine, respectively. Uptake, reduction, and storage of S and Se compounds underlie complex cellular processes that need to be understood before successful translation into improved plants for human and animal diets can be achieved. Genetic engineering, breeding, and plant production approaches use insights from cell biology and basic research to introduce tailor-made desirable traits related to S and Se metabolism. Several examples for this approach will be discussed. In terms of enhanced crop quality, the so-called push and pull approaches to improve seed S amino acid compositions draw heavily from cell biology research. In pull or sink approaches, the expression of S-rich seed storage proteins is put under the control of seed-specific promoters. Such proteins possibly carry a targeting signal for the endoplasmic reticulum to achieve deposition in protein bodies. The regulation of some health-promoting compounds of Se together with S compounds such as glucoraphanin in Brassicaceae has received considerable attention in the recent past. However, to achieve high contents of Se metabolites simultaneously with the health-promoting S-containing compounds is challenging due to the crosstalk between the two pathways. The concept of S-enhanced defence linking S nutrition of plants with enhanced synthesis of S-containing defence compounds has been supported by considerable experimental data from basic research. Some of the recent findings regarding the role and potential biotechnological applications of some of these S-containing defence compounds including glutathione, phytoalexins, and glucosinolates are discussed in this chapter. Much progress has been achieved in the enrichment of Se contents in Brassica plants, while more basic research is required to enhance seed S contents and to understand how S nutrition is linked to plant defence.