Transplantation is the process of moving cells, tissues or organs from one site to another for the purpose of replacing or repairing damaged or diseased organs and tissues. It saves thousands of lives each year. However, the immune system poses a significant barrier to successful organ transplantation when tissues/organs are transferred from one individual to another. Rejection is caused by the immune system identifying the transplant as foreign, triggering a response that will ultimately destroy the transplanted organ or tissue. Long term survival of the transplant can be maintained by manipulating the immune system to reduce the risk of rejection. Donor and recipient are carefully matched prior to transplantation to minimise the risk of rejection. They are matched based on their blood group, tissue typing, and how the recipient’s blood serum reacts to donor cells. Immunosuppressive drugs are used to prevent and to treat transplant rejection by dampening the overall immune response. However, immunosuppressive drugs are non-specific and leave patients more susceptible to disease as well as being associated with numerous unwanted side effects. Further research on the immunological mechanisms of rejection will help improve cross matching, diagnosis and treatment, as well as facilitating the discovery of novel strategies for preventing.