Thromboembolism occurs more frequently in newborns than in older infants or children. The developing hemostasis system of neonates has decreased concentrations of procoagulant proteins and the naturally occurring anticoagulants and hemostatic control proteins. Overall, neonatal hemostasis provides protection from excessive bleeding at the expense of an increased risk for thromboembolism. Intensive medical care for premature and ill infants often requires central vascular assess, and the most frequent risk factor for thromboembolism is the presence of an indwelling vascular catheter. Management of venous thromboembolism in the newborn period varies depending on the location and extent of the thrombus as well as the risk for acute embolic complications and later vascular compromise. Therapeutic decisions are guided by practitioners' past experience, published case reports and case series, several large registries, and extrapolation from results of clinical trials in adults with thromboembolic disease. Valuable consensus guidelines have been compiled by the AACP Conference on Antithrombotic and Thrombolytic Therapy. Heparin, either unfractionated or a low molecular weight preparation, is the most commonly utilized anticoagulant to treat thromboembolism in newborn infants. Thrombolytic therapy may be considered if the thrombus is life or limb threatening and there is no hemorrhagic contraindication. Multicenter, prospective, controlled clinical trials in this important patient population are needed to provide evidence-based data to better inform optimal management.