The presence of antiphospholipid antibodies has been associated with an increased risk of recurrent pregnancy loss, and there is evidence to suggest that antithrombotic therapy improves the likelihood of a successful outcome in affected women. Recent studies suggest an association between hereditary thrombophilia and pregnancy loss, although a causal role remains controversial. Although the available data are limited and flawed, there is increasing use of antithrombotic therapy in thrombophilic women with a history of pregnancy failure. Given the absence of proven effective therapy in women with unexplained recurrent loss, there is also growing pressure to intervene with antithrombotics in women with no known underlying thrombophilia. This article reviews the evidence for an association between thrombophilia and recurrent pregnancy loss and the data regarding the use of antithrombotic therapy for prevention of loss—an area that remains particularly challenging because of the paucity of good quality data upon which to base clinical decisions.