Novel imaging modalities play a major role in the preoperative staging and restaging of prostate cancer patients with aggressive diseases. The availability of cancer-specific tracers and intraoperative detectors allowed for the introduction of imaging-, fluorescence- or radio-guided approaches in the surgical setting. These tools can assist physicians intraoperatively in the precise identification of suspicious spots and for the detection of metastatic sites in the lymph nodes even outside the anatomically-defined template in patients with more advanced diseases. This, in turn, could have important implications for the correct staging of the disease and for maximizing local disease control.