High-risk pregnancy is the most common clinical association with antiphospholipid antibodies; the principal manifestations are pregnancy loss and early preeclampsia. Membership in this family of antibodies is continually growing and includes antibodies against a variety of phospholipids, phospholipid-protein complexes, and phospholipid-binding proteins. The current information in the literature is inadequate to clearly implicate a subgroup of antiphospholipid antibodies or a particular pathophysiologic mechanism as being responsible for poor pregnancy outcomes. It is clear, however, that prevalent diagnostic tests for LA and aCL are extremely useful to identify many of these patients, but are inadequate for diagnosis of all patients with autoimmune pregnancy loss or to elucidate the pathophysiology. Many patients who present clinically with autoimmune-like pregnancy complications currently are negative in tests for LA or aCL, but have antibodies against annexin V, phosphatidylserine, or other relevant antigens. The greatest risk for a complicated pregnancy is conveyed by a subgroup of antibodies that affect the normal function of placental trophoblast. As clinical laboratory tests designed to detect more members of the antiphospholipid antibody family become available, understanding of this complicated disease (APS) will increase.