Urokinase, previously used to restore patency to thrombosed haemodialysis catheters, is now unavailable in North America. We performed systematic reviews of four questions related to the safety and efficacy of alternative agents for catheter thrombolysis, searching Medline and the Cochrane Controlled Clinical Trials Register. In dialysis patients, large case series have documented that urokinase is safe and effective (>70 % efficacy for catheter instillation, and >80 % for systemic lysis). Experience with streptokinase is limited and allergic complications develop with repeated use. Studies of catheter instillation with 1--2 mg of tPA per lumen reported short-term success in 83--98 % of uses. One non-peer-reviewed study described 44--59 % success using systemic tissue plasminogen activator (tPA), 2.5 mg through each of 2 lumens, over 1 h. Meta-analysis of randomized comparisons of urokinase and tPA as full-dose thrombolytic agents suggested that 1 mg tPA was likely equivalent in thrombolytic potency to 36,000 units urokinase. In nondialysis populations, four case series suggested that catheter instillation with 0.5--2 mg tPA was effective and safe in reestablishing patency, and a randomized controlled trial found 2--4 mg tPA more effective than 5,000--10,000 units urokinase. No complications have been reported in any patient treated with systemic or local tPA for catheter thrombolysis. In studies of fistula thrombolysis with 5--50 mg tPA major complications occurred in one episode in 130 patients treated. This review suggests that 1--2 mg/lumen tPA is a suitable dose for catheter instillation and likely to be more effective than 5000 units/lumen urokinase. Systemic lysis with 5--10 mg tPA is likely to be safe and effective in suitably selected patients. Further studies are needed.