The rat model is a widely used animal model in research, its popularity perhaps only surpassed by the mouse model. Rats are the preferred models for the study of transplantation and certain tumor and autoimmune diseases. In particular, the understanding of cardiovascular-related diseases and chronic inflammation has depended widely on the rat, from which models for both multiple sclerosis and rheumatoid arthritis have been derived. Until now, research in the rat has been hampered by a lack of precise gene-targeting technology in this model. This limitation, however, is rapidly changing; a recent example is the availability of B-cell-deficient rat strains obtained by the newly established zinc finger nucleases-targeting technology. As described in this issue of the European Journal of Immunology, genetic targeting of the rat, for example, using zinc finger nucleases-targeting technology, is likely to rapidly drive progress in the understanding of not only B-cell biology but also in the general understanding of rat disease models.