It is possible to detect a genetic contribution to venous thrombosis in a significant proportion of patients. This has led to a huge expenditure in clinical time and health resource. However, the gains to be made from the uncritical investigation of the causes of venous thromboembolism are limited and the approach raises significant issues in relation to the appropriateness of this form of genetic testing. In contrast, there are some acquired prothrombotic states that should be identified because the risk of further thrombosis may be sufficient to influence therapy. These states include antiphospholipid syndrome, myeloproliferative disorders, and cancer.