This narrative review examines the translation from statistical association to change in clinical practice with respect to factor V Leiden and adverse pregnancy outcome. A collation of published meta-analyses illustrates a clear trend towards a greater association with factor V Leiden (fVL) as the severity of adverse pregnancy outcomes increases, and highlights that different study populations are relevant to different clinical scenarios. The yield of fVL testing in women with previous adverse pregnancy outcomes is up to six times higher than in the general population. Calculated post-test probabilities illustrate that the combined effect of fVL and poor pregnancy history places these women at a high-risk of recurrent events. The results to date of low molecular weight heparin (LMWH) treatment trials cannot be extrapolated to all women with thrombophilia; however, the results provide a rationale for randomized prophylactic anticoagulant treatment trials in thrombophilic women with severe adverse pregnancy outcomes. While we await the results of well-designed, adequately powered treatment trials, we propose that post-test probabilities, in addition to the preliminary treatment data in high-risk women, justify consideration of screening for fVL in women with a strong past history of poor pregnancy outcome.