The diagnosis and management of heparin-induced thrombocytopenia (HIT) in pediatric patients poses significant challenges. The cardinal findings in HIT, thrombocytopenia and thrombosis with heparin exposure, are seen commonly in critically ill children, but are most often secondary to etiologies other than HIT. However, without prompt diagnosis, discontinuation of heparin, and treatment with an alternative anticoagulant such as a direct thrombin inhibitor (DTI), HIT can result in life-and limb-threatening thrombotic complications. Conversely, DTIs are associated with higher bleeding risks than heparin in adults and their anticoagulant effects are not rapidly reversible; furthermore, the experience with their use in pediatrics is limited. Whereas immunoassays are widely available to aid in diagnosis, they carry a significant false positive rate. Age-dependent differences in the coagulation and immune system may potentially affect manifestations of HIT in children, but have not been extensively examined. In this chapter, diagnostic approaches and management strategies based on a synthesis of the available pediatric studies and adult literature on HIT are discussed.