The Toll receptor was originally identified as a regulator of embryogenesis in Drosophila. Toll-like receptors (TLRs) in mammals recognize infectious agents and other danger signals. Activation of TLRs on trophoblast influences immune cell recruitment, cytokine secretion, and decidual responses to invading pathogens during pregnancy. Importantly, biological effects of TLR signal transduction at multiple maternal-fetal interfaces may contribute to several pregnancy pathologies associated with placental dysfunction, including pre-eclampsia, intrauterine growth restriction, and preterm labor. We herein discuss mechanisms by which TLRs regulate the maternal immune response during normal and abnormal gestation, and we highlight recent data that assign a role to TLRs in the pathophysiology of selected pregnancy-associated complications.