Tumor-specific fluorescence labeling is promising for real-time visualization of solid malignancies during surgery. There are a number of technologies to confer tumor-specific fluorescence. Antibodies have traditionally been used due to their versatility in modifications; however, their large size hampers efficient fluorophore delivery. Nanobodies are a novel class of molecules, derived from camelid heavy-chain only antibodies, that have shown promise for tumor-specific fluorescence labeling. Nanobodies are ten times smaller than standard antibodies, while maintaining antigen-binding capacity and have advantageous features, including rapidity of tumor labeling, that are reviewed in the present report. The present report reviews special considerations needed in developing nanobody probes, the status of current literature on the use of nanobody probes in fluorescence guided surgery, and potential challenges to be addressed for clinical translation.