For patients with newly diagnosed prostate cancer, clinical tumour stage, Gleason score of the diagnostic biopsy specimen and serum prostate-specific antigen (PSA) level can be combined to identify a group of men at increased risk of treatment failure after radiotherapy or radical prostatectomy. For these high-risk, but still clinically localised prostate cancers, multimodal treatment strategies may result in improved cancer control outcomes. Indeed, in the setting of clinical stage T3 - T4 tumours, the combination of radiotherapy followed by hormonal therapy has improved patient survival. The benefits of adjuvant or neoadjuvant hormonal and/or chemotherapy followed by radical prostatectomy in this setting are unclear, but are the subject of ongoing or planned Phase III clinical trials. These studies will help define the role of multimodal treatment strategies in this high-risk patient population.