BACKGROUND: Most major clinical trials have failed during the last 2 decades, including large clinical trials of secondary prevention and neuroprotection. These results suggest the presence of heterogeneity among stroke patients. Biomarker is defined as a biological molecules found in blood, other body fluids or tissues that is evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers may provide the information on the heterogeneity among patients with ischemic cerebrovascular disease. In addition, stroke biomarkers could be a guiding tool for more effective personalized therapy. MAIN CONTENTS: Three aspects of stroke biomarkers are discussed. First, the role of biomarkers in stroke patients is presented. Second, limitations of current biomarkers (especially protein biomarkers) in the stroke field are discussed with possible reasons. Lastly, types of biomarkers, including protein, genetic and microparticles, are presented with their advantages and disadvantages focusing on the importance of comprehensive approaches using various types of biomarkers. EXPECTATIONS: Although biomarkers are not recommended as a routine practice in stroke patients, there have been numerous effects to overcome current limitations. The studies reviewed herein suggest that using various biomarkers to improve the understanding of individual pathophysiologies will further promote the development of screening tool of high-risk patients, predicting model of stroke outcome and rational stroke therapy tailored to the specifics of each case.