PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.