Immune-mediated inflammation and allograft rejection are greatly reduced in certain organs, a phenomenon called 'immune privilege'. Immune privilege is well developed in three regions of the body: the eye, the brain and the pregnant uterus. Immune-mediated inflammation has devastating consequences in the eye and brain, which have limited capacity for regeneration. Likewise, loss of immune privilege at the maternal-fetal interface culminates in abortion in rodents. However, all three regions share many adaptations that restrict the induction and expression of immune-mediated inflammation. A growing body of evidence from rodent studies suggests that a breakdown in immune privilege contributes to multiple sclerosis, uveitis, corneal allograft rejection and possibly even immune abortion.