Immunosuppressants are used in organ transplantation to prevent and control rejection. These drugs have inhibitory effects on both normal and abnormal immune reactions. 1. Azathioprine era: In 1954, the first human identical twin kidney transplantation was successful; the first human liver transplantation was successful in 1963. However, organ transplantation failed to gain widespread popularity in the following decade or so because of the ensuing immune response triggered by the foreign graft in the immune system of the transplant recipient after organ transplantation, an effect known as rejection. The consequence is that the graft is destroyed. In the search for measures to modulate the recipient’s immune response, azathioprine was first applied in the 1960s, but until the late 1970s, the 1-year survival rate of azathioprine combined with prednisone for kidney transplantation was only about 50%, and the results were not sufficient for successful liver and other organ transplantation. In addition, these drugs have some toxicity: mainly the inhibition of the bone marrow hematopoietic system and gastrointestinal mucosal damage. 2. Cyclosporine A era: In 1978, cyclosporine A was used for the first time in clinical kidney transplantation, and satisfactory results were achieved, with a significantly higher survival rate. The introduction of cyclosporine A was a milestone of modern organ transplantation, and its clinical application was the most significant progress of organ transplantation in the past 20 years. 1981, the combined application of cyclosporine A and prednisone in liver transplantation was a breakthrough that enabled most of the transplant recipients to survive for a considerable period of time, and the transplantation of various organs was widely carried out. 3, Pulcoflora era: FK506 was extracted in 1984, and the relevant clinical application literature was published in 1989. Recent studies have shown that FK506 has many advantages, without increasing the incidence of major side effects such as renal failure and infection, while the incidence of acute rejection and re-transplantation rates are reduced. The survival rate of transplant patients and graft survival rates have increased. In conclusion, organ transplantation has increasingly become a routine tool, and efforts to study highly efficient and less toxic immunosuppressive agents will certainly play an important role in promoting organ transplantation.