Despite recent advances in the understanding of the cellular and molecular biology of prostate cancer, new options for the treatment of prostate cancer remain elusive. Targeted therapies have shown promising activities in many solid tumours and the growing number of targets and targeted agents is creating numerous opportunities for clinical research in advanced prostate cancer. At ASCO 2006 in Atlanta, a clinical science symposium on novel targets in prostate cancer was presented. It consisted of three abstracts, each of which was followed by a discussant who reviewed the work and placed it in the overall context of current approaches to treating prostate cancer. The three abstracts were a discussion of a new method for quantification of the androgen receptor; the impact of high-dose vitamin D plus chemotherapy on hormone refractory disease and on the risk of thromboembolic disease; and the paradoxical effects seen with the raf-kinase and vascular endothelial growth factor inhibitor sorafenib, which produced improvement in bone scans in the absence of any prostate-specific antigen responses.