Although dose escalation protocols have improved biochemical control in prostate cancer radiotherapy, 10–45% of patients will experience disease recurrence. The prostate and seminal vesicles are the most frequent site of the first relapse. Traditionally, these patients have been managed with hormonal therapy, which is not curative. Recent improvements in diagnostic tests (e.g., multiparametric magnetic resonance and molecular imaging, including PET/CT scan with choline or Ga-PSMA) and new treatment techniques (e.g., stereotactic body radiation therapy or other minimally invasive alternatives like high-intensity focus ultrasound, cryoablation or high-dose-rate brachytherapy) offer new therapeutic strategies with the potential to cure some patients with limited adverse effects. In this narrative review, the authors present the most recent evidence to help identify the most suitable candidates for salvage treatment.