Abstract Context Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option. Objective We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies. Evidence acquisition A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Evidence synthesis Positive surgical margins in SRP varied from 43% to 70% in earlier publications versus 0–36% in recent publications, and pathologic organ-confined disease (OCD) was found in 22–53% versus 44–73% in earlier versus recent publications. Biochemical recurrence–free probability after SRP ranged from 47% to 82% at 5 yr and from 28% to 53% at 10 yr. Cancer-specific survival (CSS) and overall survival varied from 70% to 83% and 54% to 89% at 10 yr. Pre-SRP prostate-specific antigen value and prostate biopsy Gleason score were the strongest prognostic risk factors for progression-free survival, OCD, and CSS. Open, laparoscopic, and robotic techniques were shown to be feasible in the hands of experienced surgeons. The most frequent complications included anastomotic stricture (7–41%) followed by rectal injury (0–28%). Major complications (modified Clavien classification grade 3–5) varied from 0% to 25%. Most complications were less frequent in more recent series, except for anastomotic stricture. The majority of patients had erectile dysfunction prior to SRP (50–91%) and 80–100% after SRP. Urinary continence ranged from 21% to 90% after surgery. Limitations of this review include the absence of prospective studies and lack of comparative analyses between SRP and other therapies. Conclusions In selected patients with confirmed, localized, radiation-recurrent PCa, SRP may effectively promote durable cancer control with acceptable associated surgical morbidity and variable functional recovery.