In the last few decades we found a number of data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular, recurrent pregnancy loss (RPL). In this review several factors involved in pathophysiology of RPL related to thrombophilia were evaluated. Inherited thrombophilia due to clotting inhibitors deficiency or to clotting factors gene variants as prothrombin A20210G and factor V Leiden were firstly evaluated. Thereafter, acquired thrombophilic conditions, such as antiphospholipid syndrome or acquired activated protein C resistance or increased levels of factors VIII, were described. At last, the role of combined thrombophilic defects in pathophysiology of RPL or LPL was described.