There are many theories regarding the nature of the immune self. However, existing theories have not accounted for the clinical experience of transplantation. Kidney transplantation provides a unique opportunity to examine the nature of the immune self because the immune system is deliberately engaged at a known point in time. The self-nonself theory provides a dichotomy that is very useful for pre-transplant preparation but it fails to provide sufficient explanation for the diversity of post-transplant phenomena. The liquid self hypothesis provides a more adequate explanation for the variation in post-transplant outcomes because it accounts for the spatiotemporal evolution of the immune self in response to the environment. The immune self is always changing. The switch between self and nonself status for all antigens is the essence of the continuing change in the immune self.The success of transplantation is determined by how well the immune self adapts to the challenge that a transplant imposes.