Investigators have dedicated considerable effort to understanding the molecular basis underlying Fanconi Anemia (FA), a rare human genetic disease featuring an extremely high incidence of cancer and many congenital defects. Among those studies, FA group D2 protein (FANCD2) has emerged as the focal point of FA signaling and plays crucial roles in multiple aspects of cellular life, especially in the cellular responses to DNA damage. Here, we discuss the recent and relevant studies to provide an updated review on the roles of FANCD2 in the DNA damage response.