Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive poultry disease caused by the infectious bursal disease virus (IBDV), which causes severe economic losses to the global poultry industry. IBDV suppresses the host’s antiviral response and induces apoptosis of B lymphocytes in the bursa of Fabricius (BF), directly compromising the immune system. This impairment increases the risk of secondary microbial infections and vaccine failures. Additionally, the virulence factors of IBDV play a pivotal role in the virus’s ability to evade host defenses and survive as a successful pathogen. Notably, IBDV’s genome, characterized by two linear RNA segments, exhibits high variability and recombination properties, often leading to the emergence of variant strains in field settings. The recent emergence of novel variant IBDV strains has challenged the efficacy of existing vaccines, causing severe immunosuppression in poultry. Therefore, a thorough understanding of the viral characteristics and genetic insights into its genome variability, along with the roles of viral proteins and cellular microRNAs (miRNAs) in host response, is essential to elucidate the mechanisms of IBDV infection and pathogenesis. Such knowledge will be a great help to the rational design of safer and more effective vaccines. This chapter focuses mainly on our current understanding of the IBD pathogen, the virus-host interactions during IBDV infection, the pathogenesis of IBDV infection, and the control of IBD by vaccination.