Defining men at high risk for prostate cancer treatment failure and death continues to evolve. Identifying these men allows for better disease prognostication, patient decision treatment making and facilitates accrual for appropriate clinical trials. Men at traditional high risk for prostate cancer progression and death include men with advanced clinical stage, higher levels of PSA and Gleason pattern 4. Utilizing accepted methods of risk stratification including nomograms can aid in case identification. Softer risk factors such as obesity, race, socioeconomic status, and genetic polymorphisms are increasingly being studied. Ultimately high-throughput genomics will aid in identification of these men.