Venous thromboembolism is a common medical condition in both out-patients and in-patients. Despite the development of non-invasive tests, the diagnosis of deep vein thrombosis and pulmonary embolism remains a clinical challenge. In an effort to improve diagnostic accuracy and to reduce the necessity of serial testing, laboratory markers of thrombin generation and fibrinolysis have been investigated as first-line screening tests. Although the majority of markers are elevated in acute thrombosis, D-dimer, a specific derivative of cross-linked fibrin, appears to have the most potential clinical utility. Accuracy studies and preliminary management trials suggest that rapid D-dimer enzyme-linked immunosorbent assays and the whole blood agglutination assay, SimpliRED D-dimer (Agen Biomedical, Brisbane, Australia), have strong potential as exclusionary tests in patients with suspected venous thrombosis.