The major histocompatibility complex (MHC) is a genetic region that has been extensively studied by immunologists, molecular biologists, and evolutionary biologists. Nevertheless, our knowledge of how the MHC acquired its present-day organization is quite limited. The recent discovery that the mammalian genome contains regions paralogous to the MHC has led us to the proposal that the MHC region of jawed vertebrates arose as a result of ancient chromosomal duplications. Here, I review the current status of this proposal.