Women with antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) are at high risk for recurrent spontaneous miscarriage and late pregnancy complications, such as preeclampsia and preterm labor. Recent clinical and experimental observations suggest that the pathophysiology of pregnancy failure in patients with APS may involve inflammation at the maternal-fetal interface and disruption of normal trophoblast function and survival, rather than a pro-thrombotic event. While treatment with heparin and aspirin from early pregnancy has been shown to significantly increase the live birth rate in recurrent miscarriage patients with APS, the incidence of severe late pregnancy complications still remains high. This review will discuss what is currently known about the mechanisms by which aPL may compromise pregnancy outcome.