The diagnosis of venous thromboembolism relies on the sequential use of diagnostic tests, in validated diagnostic algorithms, based on the prior assessment of the pretest probability. Main diagnostic tests are D-Dimer and lower limb vein compression ultrasonography for deep vein thrombosis; and D-Dimer, computed tomography pulmonary angiography or lung ventilation perfusion scan for pulmonary embolism. These diagnostic strategies allow avoiding the use of the historical reference tests for venous thromboembolism, i. e. phlebography and pulmo- nary angiography. Several challenges persist, including the diminution in the prevalence of the disease among suspected patients, the management of small/distal vein thrombosis and pulmonary emboli, and diagnostic strategies in special populations, such as elderly patients, pregnant women, and patients with a prior episode of venous thromboembolism.