Solid organ transplantation is a valuable therapeutic modality for a variety of end-organ diseases. The success of this therapy is largely a consequence of the development of modern immunosuppressive agents. However, these agents also lead to significant side effects that have not reduced the development of chronic rejection. Hence, modalities that induce transplantation tolerance would be of great benefit to solid organ transplant recipients. Most studies that have examined the mechanisms involved in transplantation tolerance have focused on adaptive immunity. Over the last 10 years, there has been an increasingly large appreciation of the importance of the innate immune system in immunological responses. This review will highlight recent experimental articles that investigate the role of the Toll-like receptors, which are critical innate immune receptors, in the induction of transplantation tolerance.