This review summarizes current knowledge about the role of hereditary hypercoagulation factors predisposing to thrombophilia-associated recurrent fetal loss. Thrombophilias are a major cause of adverse pregnancy outcome, playing a role in the etiology of up to 40% of cases worldwide. Hereditary thrombophilic predispositions to recurrent pregnancy wastage include genetic lesions in blood coagulation factors II and V as well as natural anticoagulants antithrombin, protein C and protein S. Furthermore, these gene defects confer higher thrombophilia risk in combination. They, as well as the newly described annexin A5 gene M2 promoter allele are associated with repeated fetal loss. The review gives a concise description of the molecular defects arising from the genetic changes, of the role these factors play in the timing and definition of fetal loss, and risk estimates from available studies and meta-analyses. This knowledge is instrumental for a more precise assessment of individual risks for repeated fetal loss and should guide therapeutic strategies, where relevant. Since the average childbearing age increases in western societies, the importance of a timely diagnosis of fetal loss predisposition is increasing.