Prostate specific antigen (PSA) is the marker of choice in the management of prostate cancer. However, PSA is not a simple molecule, existing in the serum in five isoforms and a number of molecular configurations and complexes. The elucidation of the biochemistry of PSA has increased the potential use of the marker in the diagnosis of prostate malignancy. This review summarizes the clinical use of PSA in the management of prostate disease and the assays available in the UK. Assay calibration in relation to the World Health Organization 1st International Standard for Prostate Specific Antigen (90:10) has increased conformity between the various commercial assay kits, and the non-equimolar kits have largely been superseded or withdrawn. Special reference is made to evaluations performed on behalf of the Medical Devices Agency of the Department of Health.