Fusarium graminearum causes fusarium head scab or blight disease of cereals. Humid and moist weather conditions facilitate its epidemics leading to a high loss of grain yield and quality. The infected grains are also contaminated with mycotoxins, deoxynivalenol (DON), and nivalenol (NIV), which harm humans and animals. Wheat responds to the initial infection of F. graminearum by enhancing defence mechanisms such as thickened cell walls, dead of the affected tissues and cells, or by limiting the spread of fungal growth in the plant tissue. Farmers have successfully controlled wheat head scab fungus using systemic fungicides, including carbendazim, tebuconazole, phenamacril, and fludioxonil fungicides. Increased occurrence of this disease in the field has led to frequent use of these fungicides, which has resulted in the emergence of fungicide resistance. Understanding the processes involved in the growth, sporulation, virulence, and fungicide sensitivity of F. graminearum are essential for developing effective control measures to combat the infection. This review will focus on the regulatory mechanisms that control wheat-Fusarium graminearum interactions, development, pathogenesis, deoxynivalenol (DON) production, and sensitivity of fungicides.