Venous thromboembolism (VTE) encompasses deep-vein thrombosis (DVT) and pulmonary embolism. VTE is the leading cause of lost disability-adjusted life years and the third leading cause of cardiovascular death in the world. DVT leads to post-thrombotic syndrome, whereas pulmonary embolism can cause chronic pulmonary hypertension, both of which reduce quality of life. Genetic and acquired risk factors for thrombosis include non-O blood groups, factor V Leiden mutation, oral contraceptive use, hormone replacement therapy, advanced age, surgery, hospitalization and long-haul travel. A combination of blood stasis, plasma hypercoagulability and endothelial dysfunction is thought to trigger thrombosis, which starts most often in the valve pockets of large veins. Animal studies have revealed pathogenic roles for leukocytes, platelets, tissue factor-positive microvesicles, neutrophil extracellular traps and factors XI and XII. Diagnosis of VTE requires testing and exclusion of other pathologies, and typically involves laboratory measures (such as D-dimer) and diagnostic imaging. VTE is treated with anticoagulants and occasionally with thrombolytics to prevent thrombus extension and to reduce thrombus size. Anticoagulants are also used to reduce recurrence. New therapies with improved safety profiles are needed to prevent and treat venous thrombosis. For an illustrated summary of this Primer, visit: http://go.nature.com/8ZyCuY.