Androgen ablation therapy is the mainstay treatment of patients who have failed local therapy for prostate cancer. PSA is a serum marker commonly used to monitor patients who have undergone primary therapy for evidence of disease progression. However, there currently is no standard therapy for patients once they have demonstrated disease progression. We report a case of a 65-year-old man with castrate testosterone levels but a rising serum PSA level without radiographic evidence of metastasis. After failing prior antiandrogen therapy, he enrolled on a clinical trial comparing a PSA-based vaccine with nilutamide. When his PSA level rose on nilutamide, he commenced treatment with the vaccine therapy. He has continued to have a PSA response with the vaccine treatments with no radiographic evidence disease for >20 months.