Antiphospholipid antibodies are autoantibodies that react with phospholipid-binding proteins, chiefly b2 glycoprotein I, and are associated with thrombotic disease in men and women. These autoantibodies are also associated with a variety of pregnancy complications including stillbirth, recurrent miscarriage and they are the strongest maternal risk factor for preeclampsia increasing a woman’s risk for this disease 9 fold. Given the association with systemic thrombotic disease, for many years it was believed that antiphospholipid antibodies caused pregnancy complications via thrombosis of the maternal spiral arteries leading to infarction of the placenta and fetal demise. While this might explain some cases of stillbirth associated with antiphospholipid antibodies, thrombosis of the spiral arteries cannot explain the association with early miscarriage or preeclampsia. b2 glycoprotein I is abundant in the blood but is also expressed by placental trophoblasts and since this antigen for antiphospholipid antibodies is expressed in the trophoblasts f the placenta many teams have demonstrated multiple adverse effects of antiphospholipid antibodies on trophoblast functions in vitro. These investigations have focused largely on the effects of antiphospholipid antibodies on mononuclear trophoblasts. The human placenta contains several subtypes of trophoblasts but relatively few mononuclear trophoblasts are in direct contact with the maternal blood. Whereas, the syncytiotrophoblast is a single multinucleated cell which covers the entire surface of the placenta and is in direct contact with the maternal blood. Few workers have examined the effects of antiphospholipid antibodies on the syncytiotrophoblast. We have recently demonstrated that antiphospholipid antibodies interact with and affect mononuclear cytotrophoblasts differently to syncytiotrophoblast. In vitro, both monoclonal antiphospholipid antibodies and patient-derived antibodies are rapidly internalised into the syncytiotrophoblast. Once internalised into the syncytiotrophoblast the antiphospholipid antibodies induce alterations in life-cycle of the syncytiotrophoblast leading to a more necrotic death of this cell layer which may have adverse consequences for the mother. In contrast antiphospholipid antibodies appear to interact with the surface of mononuclear trophoblasts with a variety of consequences on the functions of these cells. Cumulatively these effects of antiphospholipid antibodies on different trophoblast populations may explain how these autoantibodies cause a wide range of clinical problems in pregnancy.