The role of MRI contrast agents is evolving, from enhancing tissue contrast to sensing physiological changes. New generation of MRI biosensors can detect and response to biomarkers such as small molecules, metabolites, metal ions, proteins, enzymes or pH. The major hurdles in translating these biosensors from bench to bedside are their insufficient sensitivity and specificity in vivo. Various biosensors have addressed these issues in specific biomedical applications. In this talk, we will discuss the frontier MRI biosensor designs for imaging biomarkers in vivo, such as using nanomaterials and MRI contrast mechanisms to improve the sensitivity and specificity, and their features to overcome barriers in biomedical applications.