This article about antithrombotic therapy in children is part of the 7th American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh the risks, burden, and costs. Grade 2 suggests that individual patients’ values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S–187S). Among the key recommendations in this article are the following. In neonates with venous thromboembolism (VTE), we suggest treatment with either unfractionated heparin or low-molecular-weight heparin (LMWH), or radiographic monitoring and anticoagulation therapy if extension occurs (Grade 2C). We suggest that clinicians not use thrombolytic therapy for treating VTE in neonates, unless there is major vessel occlusion that is causing the critical compromise of organs or limbs (Grade 2C). For children (ie, > 2 months of age) with an initial VTE, we recommend treatment with IV heparin or LMWH (Grade 1C+). We suggest continuing anticoagulant therapy for idiopathic thromboembolic events (TEs) for at least 6 months using vitamin K antagonists (target international normalized ratio [INR], 2.5; INR range, 2.0 to 3.0) or alternatively LMWH (Grade 2C). We suggest that clinicians not use thrombolytic therapy routinely for VTE in children (Grade 2C). For neonates and children requiring cardiac catheterization (CC) via an artery, we recommend IV heparin prophylaxis (Grade 1A). We suggest the use of heparin doses of 100 to 150 U/kg as a bolus and that further doses may be required in prolonged procedures (both Grade 2 B). For prophylaxis for CC, we recommend against aspirin therapy (Grade 1B). For neonates and children with peripheral arterial catheters in situ, we recommend the administration of low-dose heparin through a catheter, preferably by continuous infusion to prolong the catheter patency (Grade 1A). For children with a peripheral arterial catheter-related TE, we suggest the immediate removal of the catheter (Grade 2C). For prevention of aortic thrombosis secondary to the use of umbilical artery catheters in neonates, we suggest low-dose heparin infusion (1 to 5 U/h) (Grade 2A). In children with Kawasaki disease, we recommend therapy with aspirin in high doses initially (80 to 100 mg/kg/d during the acute phase, for up to 14 days) and then in lower doses (3 to 5 mg/kg/d for ≥ 7 weeks) [Grade 1C+], as well as therapy with IV gammaglobulin within 10 days of the onset of symptoms (Grade 1A).