TLRs have been extensively studied over the past decade for their ability to recognize microbial molecular patterns and activate innate immune cells to fight infections. They have also been described to provide a link between innate and adaptive immunity, as TLR signals also enhance the antigen presenting capacity of innate immune cells to T cells. In recent years, a contribution of TLR pathways to immune responses elicited by ischemia/reperfusion injury (IRI), allografts and xenografts has been uncovered, although the ligands that bind TLRs in these settings remain to be revealed. Such research has the potential to identify novel therapeutic targets that may facilitate allograft acceptance. In this review, we will summarize the results published to date on the role of TLRs in experimental and clinical transplantation.