The widespread use of indwelling intravascular catheters, such as central venous lines and umbilical vessel catheters, has resulted in an increased number of thrombotic complications and subsequently a growing need for specific thrombolytic therapy. The use of thrombolytic agents that have a high incidence of systemic fibrinolysis is of concern, however, especially in premature neonates. Tissue plasminogen activator is a locally acting thrombolytic agent that occurs naturally in the body. Tissue plasminogen activator can now be mass-produced through recombinant DNA technology. Reports of recombinant tissue plasminogen activator use in neonates are beginning to appear in the literature. This thrombolytic agent appears to be promising for the local lysis of clots within systemic coagulopathy. However, there is a need for controlled studies of thrombolytic agents in the neonatal population.