Rapid diagnosis of stroke is necessary for the timely delivery of thrombolysis and evaluation of novel therapies such as neuroprotection. An accurate clinical history and competent examination are key to identifying which patients are likely to have had a stroke and arranging and interpreting neuroimaging. Stroke symptoms are typically acute in onset, but are highly variable depending on the vascular territory affected. Common presenting symptoms are limb weakness, and speech and visual disturbances. Common stroke mimics are seizures, space occupying lesions, syncope, somatization and delirium secondary to sepsis. Stroke recognition instruments can help nonspecialists in the early diagnosis of stroke, with studies reporting sensitivity of over 90% and specificity of approximately 85% for some instruments. In patients with a clinical diagnosis of stroke, brain computed tomography or MRI is required to exclude some stroke mimics and differentiate ischemic from hemorrhagic stroke, which is key to providing appropriate therapies such as thrombolysis. In the future, plasma biomarkers may improve clinical diagnosis of stroke, but prospective studies are required to establish their utility. Clinical trials of acute stroke therapies need to ensure rapid accurate diagnosis of stroke using structured clinical assessments and appropriate imaging to achieve early treatment and avoid entry of stroke mimics into trials.