Thrombolysis for acute ischemic stroke has revolutionized stroke medicine. The only agent licensed for clinical use is the tissue plasminogen activator alteplase. A considerable evidence base confirms clinical and economic efficacy of alteplase use in selected patients. Meta-analyses suggest that for every 100 patients treated within 3 h, 32 will achieve a better outcome, while only three will suffer an important bleeding complication. These good-quality trial data are complemented by over a decade's worth of clinical experience that confirms the efficacy and safety of alteplase. Studies designed to enhance efficacy are ongoing. Unfortunately, current rates of thrombolysis remain disappointingly low. Thus, while novel approaches to lysis administration are welcome, strategies to improve lay-public and medical awareness of acute stroke and potential treatments are also required.