It has been almost 15 years since the publication of the landmark National Institute of Neurological Disorders and Stroke tissue plasminogen activator (NINDS-tPA) trial. The findings of the NINDS-tPA trial soon led to Food and Drug Administration (FDA) approval for IV alteplase (tPA) in the treatment of acute ischemic stroke (AIS) that transformed the way neurologists approach this devastating disease. Unfortunately, 15 years removed from the NINDS-tPA trial, IV tPA remains the only FDA-approved drug for the treatment of AIS. Although no major clinical breakthrough has occurred in the AIS treatment front, newer trials have increased the spectrum of patients who can be treated, but failed to find better lytic drugs or ways to identify treatable patients using advanced imaging. Major advancements have transpired in the arena of stroke prevention, especially in endovascular therapy and management of atrial fibrillation (AF). This article aims to summarize 5 new topics in stroke treatment, prevention, and poststroke care that have or will soon affect clinical treatment of stroke patients, and to offer critiques and commentary on how the results of the trials presented can be applied to the care of individual stroke patients (Full text).