Fusarium head blight (FHB), or scab, for its devastating nature to wheat production and food security, has stimulated worldwide attention. Multidisciplinary efforts have been made to fight against FHB for a long time, but the great progress has been achieved only in the genomics era of the past 20 years, particularly in the areas of resistance gene/QTL discovery, resistance mechanism elucidation and molecular breeding for better resistance. This review includes the following nine main sections, (1) FHB incidence, epidemic and impact, (2) causal Fusarium species, distribution and virulence, (3) types of host resistance to FHB, (4) germplasm exploitation for FHB resistance, (5) genetic control of FHB resistance, (6) fine mapping of Fhb1, Fhb2, Fhb4 and Fhb5, (7) cloning of Fhb1, (8) omics-based gene discovery and resistance mechanism study and (9) breeding for better FHB resistance. The advancements that have been made are outstanding and exciting; however, judged by the complicated nature of resistance to hemi-biotrophic pathogens like Fusarium species and lack of immune germplasm, it is still a long way to go to overcome FHB.