Patients with clinical or pathologic locally advanced prostate cancer (LAPC) are at risk for systemic and local disease progression or relapse. Pre- and post-therapy predictors of risk include prostate-specific antigen (PSA) levels, clinical and pathologic stage, Gleason's score (GS) of the biopsy and prostatectomy specimens, positive margins, and post-therapy PSA kinetics. Combined modality trials have been done predominantly in LAPC patients treated with radiation. The data indicate a local control and disease-free survival advantage to the use of androgen deprivation. Neoadjuvant hormonal therapy with radical prostatectomy (RP) has no proven role thus far; however, recent data on adjuvant hormonal therapy in patients with pathologic D1 disease treated with radical prostatectomy suggest a potential benefit. Chemotherapy trials are still in their infancy but present exciting opportunities for future research. The heterogeneity in the hormone responsiveness of prostate cancer, the availability of several active chemotherapy combinations, and the refinement in risk prediction have stimulated a series of adjuvant therapy trials which constitute the subject of this discussion. Emphasis on enrollment in clinical trials is thus imperative in LAPC.