Prostate Specific Antigen (PSA), also known as . is a 33 KD single-chain serine proteinase. The protein is regulated by androgen, mainly secreted by the epithelial cells of prostate gland. PSA secretion is increased during sexual activity and in conditions such as prostate cancer, prostatitis, and benign prostate hyperplasia. PSA level is also affected by weight, race and height. The major function of the proteinase is to cleave semenogelins in the seminal coagulum. Recently, other function of the protein has been found. PSA exists in serum in at least 3 different forms: free PSA, a-1-anti-chymotrypsin bounded PSA, and a-2 macroglobulin bounded PSA. Free PSA is the unbound form of prostate specific antigen (PSA). Free PSA level increases in aged male population and in prostate inflammatory and hyperplasia individuals. Some studies have suggested that the percentage of free PSA in total PSA is lower in patients with prostate cancer than those with benign prostate hyperplasia. The free to total PSA ratio is being introduced and studied as a biomarker of prostate cancer. Nevertheless, diagnostic and treatment decision should still be based on result of prostate biopsy in combination with the digital rectal exam and/or transrectal ultrasound.