There has recently been a significant change in the way we think about organ regeneration. In the adult, organ formation and regeneration was thought to occur through the action of organ-or tissue-restricted stem cells (i.e. haematopoietic stem cells making blood; gut stem cells making gut, etc.). However, there is a large body of recent work that has extended this model. Thanks to lineage tracking techniques, we now believe that stem cells from one organ system, for example the haematopoietic compartment, can develop into the differentiated cells within another organ system, such as liver, brain or kidney. This cellular plasticity not only occurs under experimental conditions, but has also been shown to take place in humans following bone marrow and organ transplants. This trafficking is potentially bi-directional, and even differentiated cells from different organ systems can interchange, with pancreatic cells able to form hepatocytes, for example. In this review we will detail some of these findings and attempt to explain their biological significance.