Background and Purpose – The diagnosis of ischemic stroke can be difficult. CT may be normal in the early stages of ischemic stroke or in patients with minor symptoms and MR is not always possible. Many blood markers have been proposed for the diagnosis of stroke in the acute setting. Methods and Results – We have systematically reviewed the diagnostic literature and found 21 studies testing 58 single biomarkers and 7 panels of several biomarkers. Although all show either a high sensitivity or specificity, there are limitations in the design and reporting of all the studies that mean no biomarker can be recommended for use in clinical practice. Conclusions – We make recommendations for the design and reporting of studies of diagnostic blood biomarkers in stroke.