Fusarium head blight (FHB) of wheat and barley became more frequent and severe in the subtropics of Brazil after the early 1990s. Similar to other regions worldwide, conservation tillage practices and shifts in climate are likely drivers of the FHB resurge in this region. Epidemiological and control studies conducted for over two decades prior to the resurge of the disease provided a basis for disease management. However, substantial knowledge of both basic and applied aspects of disease epidemiology, pathogen population biology, and disease control was obtained by combining molecular and epidemiological analysis of disease and pathogen datasets from both experiments and surveys. Our research findings suggest a distinctive condition for FHB in the Brazilian subtropics. Simulation and observational epidemiological/aerobiological studies suggested within-season weather most likely overshadowing any potential effect of previous crop in a zero-tillage region. The predominant random spatial disease patterns and evidence of a wheat kernel-born population that differs from maize stubble-borne population within a field suggests a key role of a well-mixed regional inoculum from both local and distant sources in the epidemics. The molecular identification of >1,000 strains from wheat and barley collected over the last decade uncovered an increased diversity of species and toxigenic genotypes compared to the major wheat regions worldwide, which may pose additional challenge to regional disease management and food security. Besides a dominant deoxynivalenol(DON)-producer (15-ADON chemotype) Fusarium graminearum population, nivalenol(NIV)-producing species, F. meridionale, among other minor ones within the F. graminearum species complex, are important contributor of FHB epidemics in specific regions (~ 30% frequency). A series of controlled-environment studies were designed to compare the biology and epidemiology among the DON and NIV-producing species, including: environmental effects, fertility, growth, spore production, toxigenicity, pathogenicity, cultivar resistance, and fungicide sensitivity. The resurge of the disease and the recent promulgation of maximum DON limits in wheat grain and byproducts led to an increased interest by researchers, policy makers, and food chain stakeholders. Disease, yield and mycotoxin data have been obtained from both surveys and disease control experiments. For example, a cooperative research network for fungicide evaluation, established in 2010, has provided important field data. These data are currently being used in meta-analyses to best define a cost-effective strategy for optimizing control (fungicide and number of sprays), but also in studies to develop new or improve existing models for predicting yield loss, disease risk and mycotoxin contamination. Although progresses have been made, continuing efforts and more attention to the problem focusing on mycotoxin contamination data are still needed to answer open research questions and improve management.