Fusarium head blight (FHB) disease that occurs in wheat is caused by Fusarium graminearum and is a major risk to wheat yield. Although several research efforts focusing on FHB have been conducted in the past several decades, conditions have become more critical due to the increase in its virulent forms. In such a scenario, conferring complete resistance in plants seems to be difficult for handling this issue. The phenotyping for FHB and finding a solution for it at the genetic level comprises a long-term process as FHB infection is largely affected by environmental conditions. Modern molecular strategies have played a crucial role in revealing the host–pathogen interaction in FHB. The integration of molecular biology-based methods such as genome-wide association studies and marker-based genomic selection has provided potential cultivars for breeding programs. In this review, we aim at outlining the contemporary status of the studies conducted on FHB in wheat. The influence of FHB in wheat on animals and human health is also discussed. In addition, a summary of the advancement in the molecular technologies for identifying and developing the FHB-resistant wheat genetic resources is provided. It also suggests the future measures that are required to reduce the world’s vulnerability to FHB which was one of the main goals of the US Wheat and Barley Scab Initiative.