Infectious agents have been implicated in the induction of antiphospholipid (aPL) antibodies and the development of the antiphospholipid syndrome (APS). This review focuses on the types of aPL antibodies detected in infections and addresses whether these antibodies are of clinical importance in patients with infections. Hepatitis C virus (HCV) infection is given special attention because this virus has the propensity to induce various autoimmune phenomena. Several aspects are emphasized that should be considered carefully when interpreting results. Most of the published data agree that thrombophilia is not observed in patients with infections (including HCV) because aPL antibodies are mostly the natural or nonpathogenic type. Thus, we do not recommend routinely testing for HCV in patients with APS. However, not all infection-associated aPL antibodies are cofactor independent. For instance, infections are increasingly recognized as a major precipitating condition of the catastrophic variant of APS, perhaps via mechanisms of molecular mimicry. Therefore, it may be possible to prevent this devastating evolution if the infectious process is promptly recognized and exhaustively treated.