Since the discovery of SCID mice in 1983, numerous studies utilizing these mice were carried out. These investigations can be classified into two major groups. First, the analysis of the immune defect has revealed defective V(D)J recombination and defective DNA double-strand break repair, and has lead to the identification of the candidate gene for SCID mice. Second, the use of SCID mice to explore ways to introduce a murine or xenogeneic immune system into SCID mice by taking advantage of the immune deficiency of the mice has provided an animal model to examine thein vivofunction of transferred human or murine immune cells. In this review, we summarize the recent advances made in these two areas of SCID mouse research.