Identification of early nodal recurrence after primary prostate cancer (PCa) treatment by functional imaging may guide metastasis-directed therapy such as salvage lymph node dissection (SLND). The aim of this systematic review was to assess the oncological role and the safety of SLND in the era of modern imaging in case of exclusive nodal recurrence after primary PCa treatment with curative intent. A systematic literature search in the PubMed and Cochrane databases was performed up to August 2018 according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Overall, 27 SLND series have been selected for synthesis. Prostate-specific membrane antigen or choline positron emission tomography/computed tomography was the reference detection technique. SLND was performed by open or laparoscopic approach with <10% of grade 3 or more complication rate. Mean follow-up was 29.4 mo. Complete biochemical response after SLND was achieved in 13-79.5%of cases (mean 44.3%). The 2- and 5-yr biochemical progression-free survival rates ranged from 23% to 64% and from 6% to 31%, respectively. Fiver-year overall survival was approximately 84%. Main drawbacks limiting the interpretation of the effectiveness of SLND were the retrospective design of single-center series, heterogeneity between series in terms of adjuvant treatment, endpoints, definitions of progression and study population, as well as the absence of long-term follow-up. A growing body of accumulated data suggests that SLND is a safe metastasis-directed therapy option in nodal recurrence after primary treatment. However, to date, high level of evidence is still missing to draw any clinically meaningful conclusion about the oncological impact of SLND on long-term endpoints. When imaging identifies exclusive nodal recurrent prostate cancer, surgery directed to the positive lesions is safe and can offer at least a temporary biochemical response. The oncological role assessed by strong clinical endpoints remains uncertain. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.