The CAEP Stroke Practice Committee was convened in the spring of 2013 to revisit the 2001 policy statement on the use of thrombolytic therapy in acute ischemic stroke. The terms of reference of the panel were developed to include national representation from urban academic centres as well as community and rural centres from all regions of the country. Membership was determined by attracting recognized stroke leaders from across the country who agreed to volunteer their time towards the development of revised guidance on the topic. The guideline panel elected to adopt the GRADE language to communicate guidance after review of existing systematic reviews and international clinical practice guidelines. Stroke neurologists from across Canada were engaged to work alongside panel members to develop guidance as a dyad-based consensus when possible. There was no unique systematic review performed to support this guidance, rather existing efficacy data was relied upon. After a series of teleconferences and face to face meetings, a draft guideline was developed and presented to the CAEP board in June of 2014. The panel noted the development of significant new evidence to inform a number of clinical questions related to acute stroke management. In general terms the recommendations issued by the CAEP Stroke Practice Committee are supportive of the use of thrombolytic therapy when treatment can be administered within 3 hours of symptom onset. The committee is also supportive of system-level changes including pre-hospital interventions, the transport of patients to dedicated stroke centers when possible and tele-health measures to support thrombolytic therapy in a timely window. Of note, after careful deliberation, the panel elected to issue a conditional recommendation against the use of thrombolytic therapy in the 3–4.5 hour window. The view of the committee was that as a result of a narrow risk benefit balance, one that is considerably narrower than the same considerations under 3 hours, a significant number of informed patients and families would opt against the risk of early intracranial hemorrhage and the possibility of increased 90-day mortality that is not seen for more timely treatment. Furthermore, the frequently impaired nature of patients suffering an acute stroke and the difficulties in asking families to make life and death decisions in a highly time-sensitive context led the panel to restrict a strong endorsement of thrombolytic to the 3 hour outermost limit. The committee noted as well that Health Canada has not approved a thrombolytic agent beyond a three hour window in acute ischemic stroke.