Prostate cancer remains the second leading cause of cancer death in men and encapsulates a wide spectrum of disease. This review describes recent advances in genomic sciences and summarizes the impact of emerging molecular profiling–based clinical applications in the diagnosis and management of early and advanced prostate cancer. It addresses the controversial guidelines surrounding prostate-specific antigen–based screening for prostate cancer and summarizes the recommendations from six different agencies. This review highlights landmark clinical trials in metastatic prostate cancer, focusing on developments within the last 5 years. It also summarizes the rationale for earlier use of chemotherapy for newly diagnosed prostate cancer (chemohormonal therapy) and gives an overview of ongoing research into the development of novel genome-based therapeutics. This review contains 4 figures, 8 tables, and 74 references. Key words: castration resistant, molecular profiling, prostate cancer, screening guidelines, treatment options