The presence of antiphospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop those clinical features. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Currently, biomarkers which enable one to predict the prognosis of patients with positive aPL are not readily available. Current advances in genomics and proteomics provide the opportunity to discover novel biomarkers based on changes in concentration levels or post-translational modifications of proteins and peptides. These techniques are now being applied in various areas of medicine with very promising results. This review covers recent studies that have used this approach for a better understanding of the pathogenic mechanisms involved in the development of thrombosis in patients with antiphospholipid syndrome (APS). Although, there are very few qualified biomarkers that have arisen as a result of efforts in proteomics, it is expected that these techniques will deliver biomarkers that might ultimately identify different subgroups of APS patients with various prognoses that might have implications with respect to management and prognosis.