Antiphospholipid syndrome is a clinicopathological syndrome comprising thrombosis and/or one of several adverse outcomes of pregnancy combined with the laboratory detection of persistent antiphospholipid antibodies. The manifestations of antiphospholipid syndrome, thrombosis, and pregnancy failure are relatively common in the population so that the diagnosis is highly dependent upon the laboratory assays that detect the antiphospholipid antibodies. These antibodies can be detected by immunoassays or coagulation‐based assays. Lupus anticoagulant is the assay most strongly correlated with clinical thrombosis and ß2‐glycoprotein 1 is the most relevant antigen in this clinical syndrome. Recent attention has focused on a subset of “triple‐positive” patients who are positive for anticardiolipin, anti‐ß2‐glycoprotein 1, and lupus anticoagulant. These patients may have a higher rate of certain clinical manifestations compared to other patients with antiphospholipid syndrome. The diagnosis of antiphospholipid syndrome has therapy‐altering implications for the management of patients with pregnancy loss and both arterial and venous thrombosis.