The proper location of the tip of a central venous access device plays a crucial role in minimizing the risks potentially associated with its use. Recent guidelines strongly recommend preferring real-time, intra-procedural methods of tip location since they are more accurate, more reliable and more cost-effective than post-procedural methods. Intracavitary electrocardiography and real time ultrasound can both be applied in the neonatal setting, but they offer different advantages or disadvantages depending on the type of central venous access device. Reviewing the evidence currently available about the use of these two methods in neonates, in terms of applicability, feasibility and accuracy, it can be concluded that (a) real time ultrasound is the only acceptable methodology for tip navigation for any central venous access device in neonates, (b) intracavitary electrocardiography is the preferred method of tip location for central catheters inserted by ultrasound-guided cannulation of the internal jugular vein or the brachiocephalic vein, and (c) real time ultrasound is the preferred method of tip location for umbilical venous catheters, epicutaneo-cava catheters, and central catheters inserted by ultrasound-guided cannulation of the common femoral vein.