Very low birth weight and other critically ill neonates require prolonged vascular access, which is achieved in current practice with central venous catheters. The initiation of adequate parenteral nutrition and prolonged intravenous medications represent the most important applications. Central vascular access in neonates is associated with a high risk for mechanical, infectious and thrombotic complications. The use of central lines is the most common cause for thrombosis in neonates and infants. The management of line-related thrombosis is based on expert opinion guidelines and is largely dependent on patient symptoms and the further requirement of the catheter. This review article focuses on pathophysiology, diagnosis, and acute and long-term management of catheter thrombosis in neonates.