Research involving human hematopoietic stem cells (HSCs) has progressed at an amazing pace. By now, more than one million HSC transplantations have been carried out in more than 500 transplantation centers worldwide, HSCs have served to treat both hematologic malignancies and functional failure of bone marrow such as in aplastic anemia and hemoglobinopathies. There are three commonly used sources of HSCs: bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). In allogeneic transplantation, HSCs are harvested from a healthy donor and then intravenously infused in the recipient. It remains to be a procedure with several potential complications especially infections and GvHD which cause a high rate of mortality and morbidity. Infection can, to some extent, accelerate the progression of GvHD and the innate immune system bridges this association between them. TLRs are germline-encoded receptors that play a key role in the innate immune system when activated by microbial pathogens leading to initiate a series of signaling programs that cause organ damage and GvHD.