Locally advanced prostate cancer encompasses several disease states that vary in the risk for progression and recurrence after initial treatment. Further, the optimal treatment strategies for locally advanced prostate cancer are continuing to evolve, reflecting the complex nature of this disease state. For many patients, clinical experience demonstrates that a combined approach of locally directed therapy and systemic therapy is likely to provide better long-term outcome than single-modality therapy. Randomized studies have established hormone ablation with external-beam radiation as an important form of treatment for this group of patients. However, additional progress needs to be made, particularly in the subgroup of patients with very high-risk disease features. As the optimal integration of local and systemic treatments becomes more clearly defined, the long-term prognosis for patients with high-risk locally advanced prostate cancer will improve.