Cyanogenic glucosides are amino acid derived natural products. Among the more than 3.000 plant species known to contain cyanogenic glucosides are important crop plants like sorghum, barley, cassava, clover, flax, lotus and almonds. The biosynthetic pathway involves two membrane bound cytochrome P450s and a soluble UDPG-glucosyltransferase that are assembled in a metabolon to secure “conveyor belt” synthesis of the cyanogenic glucoside. Cyanogenic plants also contain degradative enzymes that upon cellular disruption of the plant tissue are brought in contact with the cyanogenic glucosides causing cyanide release. This binary system provides such plants with an immediate chemical defense response to herbivores and pathogens causing tissue damage. However, the trait of cyanogenesis is about 430 million years old enabling co-evolution of cyanogenic plants and their herbivores and pests. In some cases, insects are able to sequester cyanogenic glucosides present in their host plant and to use the plant derived cyanogenic glucoside in their own defence. In some instances, where insects are not able to obtain the desired amount of cyanogenic glucosides from their host plants, they are able to carry out de novo synthesis. The defence system of the plant has thus been taken over by the insect. Likewise, some fungal pathogens appear to utilize cyanogenic glucosides as host recognition factors. Accordingly, it is not obvious to predict what happens with respect to plant-herbivore and pest resistance when the pathway for cyanogenic glucoside synthesis is introduced into a new crop species or when the pathway is blocked in a cyanogenic crop plant. We have studied these intimate relationships using genetic engineering in barley, cassava, lotus and Arabidopsis.