Standard of care in the management of brain tumors primarily consists of achieving maximal safe resection, while preserving eloquent brain regions. To date, this has been accomplished by neuronavigation guided by anatomical and even functional imaging. However, such imaging modalities have only been able to assist the surgeon in accurately highlight the bulk tumor and possibly identifying solid tumors that have infiltrated into adjacent areas within the surgical field. Diffusive tumors however, are still elusive to the surgeon and are the main cause of recurrence. The diagnostic gold standard to discriminate between normal and diseased tissue of with sparse tumor cells is histopathological analysis of a biopsied sample, a time-consuming technique prone to miss-sampling errors with no possibility to provide real-time diagnosis. Therefore, replacing conventional pathological examination with a slide-free and label free technique capable of providing accurate intraoperative diagnosis in real-time will positively impact patient outcomes. We have addressed this critical need by developing a non-invasive multimodal nonlinear endomicroscope that allows real-time optical biopsy. It will provide immediate information for diagnostic use without removal of tissue and will assist the surgeon in forming the optimal strategy for resection. This instrument will combine several means of contrast. Parallel to the instrumentation development, we are currently improving our understanding of the various optical features measured by multimodal optical imaging pertaining to different biomolecules. This endeavor will allow us to create a database on the optical signatures of the diseased and control brain tissues.