We systematically reviewed the literature to explore gender issues in acute stroke thrombolysis. The literature is inconsistent regarding the influence of gender on the timing of presentation to hospital, decision-making and utilization of acute thrombolysis among ischemic stroke patients, and hence any reported gender bias may be site-specific. Without treatment with thrombolysis, female stroke patients have a poorer clinical outcome compared to their male counterparts. Although some studies show that women have better clinical outcomes than men following intravenous thrombolysis, no gender difference is seen in others. Post-hoc analyses of relatively small studies show higher recanalisation rates in women than men following intravenous thrombolysis, and no gender difference in recanalisation rates following intra-arterial thrombolysis. Future thrombolytic trials should consider the effects of gender on both surrogate and clinical outcomes.