The interaction between wheat and Hessian fly [Mayetiola destructor (Say)] is governed by two interacting mechanisms: induced susceptibility versus induced resistance. Induced susceptibility involves the formation of a carbon sink at the feeding site and elevated conversion of carbon-compounds into nitrogen-compounds. Silence of specific genes that prevent carbon-sink formation and carbon-nitrogen conversion can result in “resistant” plants that do not carry an effective resistance gene. Induced susceptibility is likely caused by a complex of effector proteins (or so called elicitors) that are injected into host plants by the insect. Analysis of the salivary secretome of Hessian fly larvae revealed a large number of genes coding for elicitor proteins. While these elicitors can manipulate the metabolic pathways of host plants, resulting in induced susceptibility, they can also be recognized by the plant’s surveillance system to initiate defense reaction, resulting in induced resistance. Induced resistance, mediated by specific resistance genes that operate in a gene-for-gene fashion, involves the fortification of cell wall, the prevention of carbon-sink formation, and the inhibition of carbon-nitrogen conversion. Similar to the elicitor genes in the insect, there are also a large number of resistance genes in wheat. Different resistance genes are also clustered within short chromosome regions and are under high selection pressure for diversification. The attack and counter-attack between the Hessian fly and wheat as well as between their symbions involve a complex of molecular interactions and co-evolutions.