Both coagulopathy and abnormal thrombosis can complicate the anesthetic and surgical management of neonatal patients; however, the patterns of bleeding and thrombosis in neonates differ from those in adults or older children. Severe coagulopathic bleeding most commonly occurs during heart surgery and almost certainly contributes to morbidity and mortality in this population. Such severe bleeding is rare during other surgery; the exception is babies presenting to the operating room with established coagulopathy secondary to severe sepsis. Alternatively, pathological thrombosis will mainly occur in association with indwelling vascular access devices or surgically created vascular shunts. There are important differences between the coagulation system in neonates and older patients. The implication of this is that therapies established in other patient groups will not be optimal for neonates without adaptation. While evidence from high-quality clinical trials is rarely available, an understanding of how coagulation in neonates differs can help to guide practice. This review will discuss important differences between the coagulation system of neonates and older patients and how these relate to newer models of coagulation. The emphasis will be on issues likely to impact on perioperative care. In particular, the management of severe bleeding, the manipulation of coagulation during heart surgery, and the management of coagulopathy in septic neonates will be discussed in detail.