Fluorescence surgical navigation helps surgeons to see molecular information about tissue near the surface and distinguish malignancies from healthy tissue. It is possible to label tumors with specific fluorescent molecules, but not to easily see into tissue beyond microscopy limits of near a millimeter. Furthermore, the molecular targeting generally suffers from poor tumor-to-background contrast due to non-specific signal from healthy tissue. Both of these challenges can be addressed by time-resolved, single-photon sensitive imaging utilizing emerging SPAD sensors. Here we review current achievements in 3D depth sensing and functional imaging in vivo, and provide guidance for further design of surgical SPAD cameras. We hypothesize that the utility of surgical guidance will grow with the combination of new fast sensors and functional fluorescence imaging methods that utilize existing FDA-approved labels.