Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (β2GP) I on trophoblast cell membranes. aPL/anti-β2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.