In recent years, management of prostate cancer has benefited from an expanding array of new pharmacological options that are the result, in part, of an increased understanding of, and ability to target, androgen signaling. Further characterization of additional molecular pathways relevant to prostate cancer tumorigenesis has identified new molecular targets in prostate cancer that may be amenable to therapeutic intervention with novel agents. In addition, novel radioisotope therapies and cytotoxic agents have shown significant anticancer efficacy with manageable patterns of toxicity, and will eventually have to be integrated into our algorithms of therapy. This review summarizes recent findings in clinical prostate cancer research reported at the 2012 Annual Scientific Meeting of the American Society of Clinical Oncology (ASCO) and addresses their relevance to clinical practice.