Objective Fluorescence guidance has a demonstrated potential in maximizing the extent of high-grade glioma resection. Different fluorophores (fluorescent biomarkers), including 5-aminolevulinic acid (5-ALA) and fluorescein, have been examined with the use of several imaging techniques. Our goal was to review the state of this technology and discuss strategies for more widespread adoption. Methods We performed a Medline search using the key words “fluorescence,” “intraoperative fluorescence-guided resection,” “intraoperative image-guided resection,” and “brain glioma” for articles from 1960 until the present. This initial search revealed 267 articles. Each abstract and article was reviewed and the reference lists from select articles were further evaluated for relevance. A total of 64 articles included information about the role of fluorescence in resection of high-grade gliomas and therefore were selectively included for our analysis. Results 5-ALA and fluorescein sodium have shown promise as fluorescent markers in detecting residual tumor intraoperatively. These techniques have demonstrated a significant increase in the extent of tumor resection. Regulatory barriers have limited the use of 5-ALA and technological challenges have restricted the use of fluorescein and its derivatives in the United States. Limitations to this technology currently exist, such as the fact that fluorescence at tumor margins is not always reliable for identification of tumor-brain interface. Conclusions These techniques are safe and effective for increasing gross total resection. The development of more tumor-specific fluorophores is needed to resolve problems with subjective interpretation of fluorescent signal at tumor margins. Techniques such as quantum dots and polymer or iron oxide-based nanoparticles have shown promise as potential future tools.