The aim of this review is to discuss the role of Toll-like receptors at the maternal-fetal interface and the capacity of trophoblast cells to initiate innate immune responses towards infection. The maternal-fetal interface represents an immunologically unique site that must promote tolerance to the allogenic fetus, whilst maintaining host defense against a diverse array of possible pathogens. Clinical studies have shown a strong association between certain complications of pregnancy and intrauterine infections. Therefore, innate immune responses against microorganisms at the maternal-fetal interface may have a significant impact on the success of a pregnancy. There is growing evidence that trophoblast cells are able to recognize and respond to pathogens through the expression of Toll-like receptors, an important part of innate immunity. This review will discuss the role of Toll-like receptors at the maternal-fetal interface, the potential for trophoblast cells to function as components of the innate immune system and the impact TLR-mediated trophoblast responses may have on pregnancy outcome.