Stroke is the third most common cause of death in the United States and it is the leading cause of disability. Early diagnosis and immediate therapeutic interventions are important factors to reduce the extent of brain tissue damage and the risk of stroke–related death. A rapid blood test that can confirm the clinical or imaging diagnosis or that can add to the stratification of the risk would be very useful. Such a test has to be validated in large studies and has to be based on a simple and low–cost technology. Many biological markers were tested for their ability to serve as ‘would–be’ stroke biological markers; some of them appear to have a place in the diagnostic work–up of stroke patients. These molecules include Glial Fibrillary Acidic Protein (GFAP), the N–methyl–D–aspartate receptor (NMDA), APO C–III, APO C–I, PARK7, nucleoside diphosphate kinase A (NDKA), S100B, B–type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase–9, and monocyte chemotactic protein–1. There are obvious limitations to this study, among them the fact that disability does not necessarily correlate with the amount of cerebral tissue lost (the site of stroke may be more important) and the role of the blood–brain barrier in delaying the release of the neuronal proteins in the blood stream. Further studies are awaited to confirm the role of these molecules in the management of acute stroke patients.