The incidence of venous thromboembolism (VTE) in children is increasing. Hospitalized infants and adolescents are at highest risk, and most individuals who have VTE have multiple thrombotic risk factors. The presence of a central venous catheter (CVC) is the most frequent risk factor for childhood thrombosis. Childhood VTE has significant consequences in relation to the thrombotic event and the anticoagulant therapy used for its treatment. Identification of the most prevalent risk factors for VTE, particularly among adolescents, has moved the focus toward prevention of thrombosis. Risk assessment models have been developed to identify individuals who are at higher risk with a view to employing preventative strategies such as mechanical and chemical thromboprophylaxis (TP). There is currently little evidence to support the efficacy of such strategies for preventing either CVC-associated thrombosis or thrombosis at other sites. In addition, there are concerns about adverse consequences of mechanical and chemical TP in a population where the overall incidence of VTE remains low.