Fusarium head blight (FHB) is one of the most devastating diseases of small grain cereals, including wheat. FHB disease compromises both the yield as well as the quality of the infected grains as a result of mycotoxin accumulation produced by its causal agent, Fusarium gramineareum (Fg). Deoxynivalenol (DON) is the most common toxin found in infected kernels. Strict limits are imposed on mycotoxin levels; therefore Fg presence can result in exclusion of grain from human or even animal consumption rendering a crop worthless. Currently, measures to control Fg are largely restricted to chemical fungicide sprays as resistant wheat varieties have proven challenging to develop. This stems from the polygenic control underlying the available FHB resistance sources in hexaploid wheat and the dearth of resistance sources available in tetraploid wheat. The complex genetic control of FHB resistance along with inconsistencies with current chemical controls necessitates additional strategies to reduce FHB incidence that can be used in parallel to breeding for improved resistance. The completion of the genome sequence for both wheat and Fg provides the foundation for new strategies to control pathogen growth by exploiting the phenomenon of Host-Induced Gene Silencing (HIGS). HIGS is a non-GMO based technology that uses sequence specificity in dsRNA molecules to transcriptionally silence target genes. The use of dsRNA molecules to silence genes that support pathogen growth and mycotoxin production might offer a viable strategy to control future FHB epidemics. Recent work examining transcriptional changes induced by FHB infection over a range of wheat varieties expressing differential levels of resistance to Fg has provided insight into the mechanisms involved in early FHB infection. Based on these results, a number of FHB genes have been identified as important in the infection process and have been selected for silencing to reduce pathogen growth and/or DON production using HIGS. Here we report on the progress of identifying Fg gene targets that can be used as future next-generation fungicides.