The ascomycete fungal pathogen Fusarium graminearum causes the globally important Fusarium head blight (FHB) disease on cereal hosts, such as wheat and barley. In addition to reducing grain yield, infection by this pathogen causes major quality losses. In particular, the contamination of food and feed with the F. graminearum trichothecene toxin deoxynivalenol (DON) can have many adverse short- and long-term effects on human and animal health. During the last decade, the interaction between F. graminearum and both cereal and model hosts has been extensively studied through transcriptomic analyses. In this review, we present an overview of how such analyses have advanced our understanding of this economically important plant-microbe interaction. From a host point of view, the transcriptomes of FHB-resistant and FHB-susceptible cereal genotypes, including near-isogenic lines (NILs) that differ by the presence or absence of quantitative trait loci (QTLs), have been studied to understand the mechanisms of disease resistance afforded by such QTLs. Transcriptomic analyses employed to dissect host responses to DON have facilitated the identification of the genes involved in toxin detoxification and disease resistance. From the pathogen point of view, the transcriptome of F. graminearum during pathogenic vs. saprophytic growth, or when infecting different cereal hosts or different tissues of the same host, have been studied. In addition, comparative transcriptomic analyses of F. graminearum knock-out mutants with altered virulence have provided new insights into pathogenicity-related processes. The F. graminearum transcriptomic data generated over the years are now being exploited to build a systems level understanding of the biology of this pathogen, with an ultimate aim of developing effective and sustainable disease prevention strategies.