Prostate-specific antigen (PSA) was discovered about 20 years ago and over the last decade it has become the premier tumor marker for diagnosis, monitoring and prognosis of prostatic carcinoma. PSA is now considered to be the best tumor marker available in clinical medicine. It is the only tumor marker that has been approved by the Food and Drug Administration of the USA for mass screening: for the purpose of diagnosing early prostatic carcinoma. Among the newest developments in the field are the discovery of the molecular forms of PSA in serum, the development of ultrasensitive assays that allow better monitoring of patients after radical prostatectomy, and the discovery of non-prostatic PSA. Indeed, there are indications that PSA might be useful for the diagnosis and prognosis of breast cancer. The genomic structure of PSA and other human kallikrein genes and the regulation of their expression has recently been elucidated. Currently, the PSA promoter and enhancer are being investigated in connection with gene therapy in prostatic tissue. Efforts are now underway to supplement the clinical value of PSA measurements with additional prostatic markers, including human kallikrein 2 (hK2) and prostate-specific membrane antigen (PSMA).