Although the optimal treatment for patients with high-risk prostate cancer remains unclear, combined radiotherapy and androgen-deprivation therapy (ADT) has become the standard of care; however, more recently, this paradigm has been challenged. In contemporary surgical series, using a multimodal approach with primary radical prostatectomy and adjuvant radiotherapy, when appropriate, had comparable efficacy in patients with high-risk disease to radiotherapy in combination with ADT. Furthermore, perioperative and postoperative morbidity associated with radical prostatectomy seem to be similar in patients with low-risk, intermediate-risk, or high-risk prostate cancer. Importantly, downstaging and downgrading of a substantial proportion of tumours after surgery suggests that many patients might be overtreated using radiotherapy and ADT. Indeed, the potential benefits of surgery include the ability to obtain tissues that can provide accurate histopathological information and, therefore, guide further disease management, in addition to local control of disease, a potentially reduced risk of developing metastases, and avoidance of long-term ADT. Thus, patients with high-risk disease should be offered a choice of first-line treatments, including surgery. However, effective management of high-risk prostate cancer is likely to require a multimodal approach, including surgery, radiotherapy, and neoadjuvant and adjuvant ADT, although the optimal protocols remain to be determined.