Although the prognosis in patients with localized prostate cancer is positive overall, high-risk localized disease is responsible for significant cancer-related morbidity and mortality following local treatment failure. Despite recent medical advances in advanced prostate cancer, the role of systemic adjuvant therapy has remained relatively stagnant over the last few decades for patients with high-risk disease, consisting of only androgen deprivation therapy. Novel methods of risk stratification, however, based on traditional clinicopathologic features combined with genomic data, will allow investigators to study adjuvant therapy with more precision in high-risk populations. Additionally, the rise of novel hormonal therapies may provide oncologists with more efficacious drugs in the adjuvant setting, potentially leading to effective adjuvant therapy options for clinicians treating men with high-risk localized prostate cancer.