Although prostate-specific antigen (PSA) has evolved as a very useful tool for detection of prostate cancer, there remains an urgent need for more accurate biomarkers to diagnose prostate cancer and predict cancer-related outcomes. Recent advances in the study of proteomics and high throughput techniques have led to the discovery of many potential biomarkers for prostate cancer. This article briefly reviews the current status of PSA testing and discusses several candidate protein biomarkers for prostate cancer, as well as highlighting some recent proteomic discoveries with the potential to supplement or even replace PSA for the diagnosis and prognosis of prostate cancer.