Antiphospholipid antibodies are a heterogeneous group of acquired autoantibodies that react with anionic phospholipids, such as cardiolipin. Anticardiolipin antibodies (ACAs) are frequently found in patients with systemic lupus erythematosus and other autoimmune disorders and can react with the phospholipid alone or bound to the cofactor beta2-glycoprotein-I. This latter form of cofactor-dependent ACAs is strongly associated with the occurrence of thrombotic events. ACAs have been observed to occur in both chronic hepatitis B and chronic hepatitis C as well as in other viral infections and in neoplastic diseases. In viral infection, ACAs are generally cofactor independent and may represent an epiphenomenon of the infection. Some studies, however, have found an increased incidence of thrombotic disorders in patients with chronic hepatitis C virus (HCV) who manifest ACA positivity suggesting that the presence of these autoantibodies may predispose to thrombosis in specific HCV-infected patients. In conclusion, ACAs are commonly found in patients with chronic viral infection but their pathogenetic role and the mechanisms that stimulate their production have not yet been clarified.