The development of immunoassays for prostate-specific antigen (PSA) and their clinical utility are summarized. Because of the complexity of the PSA molecule and anti-PSA antibodies, there is currently no standard in PSA measurement. Evaluating various immunoassays requires the knowledge of the lower limit of detection as well as the biological and clinical thresholds of a given assay. There have been recent reports demonstrating earlier detection of residual prostate cancer after radical prostatectomy by ultrasensitive assays for PSA. Because of the recent evidence for non-prostatic sources of PSA such as the male urethra, the possibility of their contaminating PSA levels must be evaluated when more sensitive assays for PSA are under consideration.