For more than 420 million years, plants, insects and microbes have co-evolved based on a chemical arms race including deployment of refined chemical defense systems by each player. Cyanogenic glucosides are one class of defense compounds produced by numerous plants (e.g. sorghum, barley, wheat, cassava, clover, flax, almonds, eucalypts). The biosynthetic pathway is catalyzed by multifunctional cytochrome P450s (CYP79 and CYP71) and a UDP-glucosyltransferase with oximes as a key intermediate. The enzymes are thought to be organized within a dynamic enzyme complex (metabolon) to ensure rapid metabolism of the toxic pathway intermediates. The genes encoding the biosynthetic enzymes are clustered on the genome. Following tissue disruption e.g. caused by a chewing insect, the cyanogenic glucosides are hydrolyzed and release toxic hydrogen cyanide to protect the plant from generalist herbivorous. Specialized insects manage to sequester cyanogenic glucosides from their food plant and to use the plant defence compound in their own defence against predators. If some cases such insects de novo synthesize the compounds if the amounts obtained by sequestering are not sufficient. Suicient levels are important because the cyanogenic glucosides play numerous additional intimate roles in the mating process of the insects. Many fungi are not deterred by hydrogen cyanide which they rapidly convert into carbon dioxide and ammonia. However, the oxygen burst associated with the fungal infection may partly inactivate the enzyme complex so that oximes with anti-fungal activity become the defense mechanism. In plants, cyanogenic glucosides serve numerous additional metabolic functions in addition to defense. They may function as storage reservoirs of nitrogen and sugar, as quenchers of reactive oxygen species and as signal molecules. Forage sorghum contains the cyanogenic glucoside dhurrin and following adverse growth conditions, the amounts of HCN released may be toxic to grazing lifestock. In collaboration with Australian researchers, biochemical screens and TILLING approaches have been used to identify a single amino acid change in the CYP79 enzyme that resulted in an inactive enzyme and acyanogenic plants. In synthetic biology approaches, we have shown that the entire pathway for cyanogenic glucoside synthesis can be moved into the chloroplast and directly driven by reducing equivalents from photosystem I.