Thrombus-related catheter malfunction is a significant problem for catheter-dependent dialysis patients. The primary medical intervention is the local luminal installation of thrombolytic agents (TLAs). There are three major TLA installation methodologies: locking, push, and infusion protocols. A systematic literature review of existing TLA protocols for treating dialysis catheter malfunction was performed using the PubMed and EMBASE (Drugs and Pharmacology) databases from the time of each database's inception to August 2005. Thrombolytic administration was then categorized according to the patient's clinical need: (1) an acute/immediate requirement, such as when malfunction prohibits dialysis initiation, and (2) rescue therapy, such as when the thrombus threatens to significantly impair current or subsequent dialysis clearance. Published TLA protocols are discussed in the context of their clinical requirement (acute or rescue therapy). A unifying clinically relevant management algorithm that considers the etiology of catheter malfunction as being thrombus related or not, and an approach to TLA use based on clinical presentation is described. This algorithm was developed after a systematic review of the literature. The application of this treatment algorithm requires prospective validation and study.