The PSA revolution that has occurred over the previous 2 decades has positively impacted the detection and treatment of men with prostate cancer. Although methods to improve specificity have shown promise (eg, PSAD, age-specific PSA, and PSA velocity), meaningful interpretation has yet to be uniformly accepted within clinical practice. The identification of other molecular forms of PSA within serum has led to a new era in PSA markers. Initial application employing %fPSA has provided improved discrimination between benign and malignant prostatic disease; however, questions remain regarding the ultimate threshold value. The discovery of various free forms of PSA--such as proPSA, BPSA, and iPSA--also have introduced the potential for improved specificity in detection. Although early results are encouraging, further evaluation is anticipated. The development of improved methods to detect and measure cPSA has demonstrated provocative results, and exhibits the potential to replace PSA as a standard diagnostic test in cancer screening.