Toll-like receptors (TLRs) belong to a family of pattern-recognition receptors for microbial products and endogenous molecules released by stressed cells. Experimental studies show that TLRs are involved in the process of acute allograft rejection and that their activation can prevent transplantation tolerance. Herein, we review the expression of TLRs and the impact of TLR signaling in different cell types in grafted organs including antigen-presenting cells, T and B lymphocytes, epithelial and endothelial cells. We then discuss the involvement of TLRs in the different phases of the rejection phenomenon and the impact of TLR-mediated events on regulatory circuits which dampen alloimmune responses.