Upper-extremity deep venous thrombosis is less common than lower-extremity deep venous thrombosis. However, upper-extremity deep venous thrombosis is associated with similar adverse consequences and is becoming more common in patients with complex medical conditions requiring central venous catheters or wires. Although guidelines suggest that this disorder be managed using approaches similar to those for lower-extremity deep venous thrombosis, studies are refining the prognosis and management of upper-extremity deep venous thrombosis. Physicians should be familiar with the diagnostic and treatment considerations for this disease. This review will differentiate between primary and secondary upper-extremity deep venous thromboses; assess the risk factors and clinical sequelae associated with upper-extremity deep venous thrombosis, comparing these with lower-extremity deep venous thrombosis; and describe an approach to treatment and prevention of secondary upper-extremity deep venous thrombosis based on clinical evidence.