Although there are a variety of treatment options for nonmetastatic androgen-independent prostate cancer (AIPC), they have limited benefits. Currently, no standard of care exists for this population. Ultimately, sequential therapeutics can be used to minimize symptomatic progression and control the underlying disease, as determined by prostate-specific antigen (PSA) levels. We report here a 90-year-old patient who had PSA progression after multiple previous treatments and was started on ketoconazole 200 mg, three times daily. His serum PSA levels dropped 84% in less than a year on therapy. A literature review yields several studies that support the benefits of ketoconazole as noted by PSA reduction and correlates these responses with survival benefits. The literature also suggests that low-dose ketoconazole may be an appropriate second- or third-line hormonal agent in AIPC, causing a PSA decline, symptomatic relief, and minimal toxicity.