Although allogeneic blood transfusion (ABT) is a valuable medical practice, it has some critical complications. One of these complications is transfusion-related immunomodulation (TRIM). Transfusion-related immunomodulation describes the changes and its results in recipient's immune system after ABT. After ABT, some outcomes may be observed in the recipient including increased graft survival, decreased Crohn's disease recurrences and recurrent spontaneous abortuses, increased postoperative bacterial infections, cancer recurrences and mortality, and reactivation of latent infections such as cytomegalovirus and human immunodeficiency virus. It has been postulated that TRIM may originate from leukocytes within the product, biologic response modifiers-immunologic mediators (BRM-IM) that accumulate within the plasma or soluble human leukocyte antigen-class I molecules within the allogeneic plasma. Also, some properties of erythrocytes, storage time of blood components, and the number of transfused products are accused of TRIM development. However, main factors held responsible for TRIM development are allogeneic leukocytes and related BRM-IMs. It is thought that mechanisms such as clonal deletion, immunosuppression, anergy, microchimerism, the polarization of the immune response from T helper 1 (Th1) to Th2 and, apoptosis in the recipient immune system may cause TRIM. For this reason, leukoreduction is suggested for prevention. However, this application may not be efficient since reasons other than leukocytes may limit leukoreduction.