The antiphospholipid syndrome is defined by the persistent presence of antiphospholipid antibodies in plasma of patients with a history of thrombosis and/or pregnancy morbidity. From the definition in 1985 onwards, confusion has arisen concerning who has the syndrome and who has not. Although the clinical criteria are well defined, there is ongoing discussion regarding serologic criteria. Lack of standardization of the assays that define the serologic criteria, notably phospholipids-dependent coagulation assays, and enzyme-linked immunosorbent assays (ELISAs) for anticardiolipin and anti-beta2 glycoprotein I, have led to heated arguments regarding which population(s) of antibodies should be measured to detect a patient at risk for (recurrent) thrombosis or pregnancy complications. Everybody agrees on the need to better standardize the assays, but different views are held on how this should be achieved, and commercial interests have hampered consensus on which assays should be applied, how they should be performed, and the cutoff values that discriminate between pathologic and nonpathologic results. New prospective cohort studies to reevaluate the clinical significance of the available assays are essential, but the lack of sufficient patient numbers visiting single hospital facilities frustrates progress. This review discusses shortcomings of the current serologic assays, provides strategies to solve these shortcomings, and discusses new developments/assays to improve the specificity of such assays for thrombosis and pregnancy complications.