Patients with high-risk and advanced prostate cancer require safe and efficacious therapies likely to offer a survival advantage while minimizing the treatment-related toxicities. Improvements in the surgical technology, diagnostic modalities, radiological staging, and risk stratification have made surgery for high-risk and advanced prostate cancer a safe and feasible option. In this review, we outline the role of radical prostatectomy in high-risk localized, locally advanced, and metastatic prostate cancer. We overview available data evaluating the use of surgery in the context of a multi-modal approach and highlight ongoing trials in this area. Furthermore, the role of surgery as a non-systemic modality for metastasis-directed therapy (MDT) is also described. Emerging imaging modalities enabling more accurate staging and longer follow-up of clinical trials for prognostic endpoints are anticipated to help identify patient cohorts and treatment strategies, where the use of surgical treatments is likely to provide oncological benefits and acceptable toxicity.