Optimal management of retinal vein occlusion (RVO) is still a matter of debate. Antithrombotic and fibrinolytic drugs have been investigated after demonstration of a role of thrombosis in the complex pathogenesis of the disease. Aim of our study was to systematically summarise best available evidence on the acute treatment and on the secondary prevention of RVO with antithrombotic and fibrinolytic drugs. A computer-assisted search of the MEDLINE and EMBASE electronic databases up to January 2009 was performed. Two review authors selected all published randomised controlled trials (RCTs) from the search, assessed study quality and extracted data. Based on Jadad's score, RCTs were stratified into three quality categories. A total of six RCTs were included. Only one RCT of high quality was identified. A total of 384 patients were investigated, 234 with central retinal vein occlusion and 150 with branch retinal vein occlusion. No study enrolled more than 100 patients. Three studies compared therapeutic doses of low-molecular-weight heparin (LMWH) with low-dose aspirin, one study compared ticlopidine with placebo and two studies compared intravenous fibrinolytic therapy followed by warfarin or aspirin with either haemodilution or no treatment. A partial improvement of visual acuity was reported in every study, independently of the study drug. No long-term secondary prevention study was published. The present systematic review suggests that antithrombotic therapy, in particular LMWH, may be part of the therapeutic armamentarium for patients with recent onset RVO. No firm recommendation can be provided given the limited available evidence.