While we are now able to diagnose inherited thrombophilias in a substantial number of patients with venous thromboembolism (VTE), the initial hope that their presence would inform recurrence risk and thus decisions on anticoagulation duration has largely been disappointing. Indeed, the presence or absence of transient provoking risk factors has proven to be the most important determinant of VTE recurrence risk. Thus, particular attention to transient acquired risk factors for VTE remains paramount, as they have generally shown to carry more prognostic weight than inherited thrombophilias. The presence of other acquired risk factors may require additional management considerations - whether pertaining to anticoagulant choice as in antiphospholipid antibody syndrome or to addressing a new predisposing medical condition as in malignancy. Antithrombin deficiency or the presence of more than one thrombophilic defect may be exceptions that can have a role in prognostication; however as illustrated in this review through several case vignettes, interpretation and clinical application of the results of inherited thrombophilia testing is nuanced. We have chosen to focus on cases in which patients have been identified as having thrombophilic defects rather than the indications for undertaking testing in the first place or the extent of investigation.Management decisions in such cases ultimatelyhinge on individualized consideration of the benefits and risks of anticoagulation along with patient preference rather than on an algorithmic pathway based on thrombophilia status.