The term "economic class syndrome" is generally used to describe the occurrence of venous thromboembolism (VTE) in travelers after long-distance airline travel in economic class. However, cases of VTE have also been reported in business class travelers and in subjects exposed to prolonged periods of immobilization while using other forms of transportation such as automobile, train, and bus. VTE manifests with deep vein thrombosis and pulmonary embolism but may also present with less severe, reversible manifestations such as headache, vertigo, and respiratory symptoms. Epidemiological studies have shown that the risk of VTE doubles following airline travel lasting longer than four hours. The risk of VTE increases with increased duration of air travel even in the presence of multiple stop-overs. In subjects with known risk factors, incidence of VTE depends on the degree of risk (low, medium, high) and on the duration of the flight. The main factor leading to VTE is prolonged immobilization and the pathogenesis is based on Virchow's triad: venous stasis, vessel wall injury, and hypercoagulability of blood. Specific characteristics of airline travel such as jet lag, low air quality and dehydration may increase the risk of VTE with respect to other forms of travel. This article discusses epidemiological aspects and pathogenesis of travel-related VTE and prophylactic measures that should be undertaken.