Some men affected with clinically localized prostate carcinoma suffer life-threatening recurrence, despite previous treatment with surgery or radiation therapy, underscoring the need for new, effective, systemic adjuvant treatment approaches. Recent molecular mechanism-based prostate cancer drug discovery efforts have identified several candidate targets for systemic prostate cancer adjuvant therapy; however, traditional cancer treatment development algorithms may not be appropriate for many of the new treatment strategies. To best exploit the clinical potential of these molecular treatment strategies, novel translational research strategies are required to support hypothesis-driven clinical research and development.