Prostate cancer is the most common neoplasia of middle-aged men. Prostate specific antigen (PSA) is the first FDA-approved tumour marker for early detection of cancer and it is now in widespread clinical use. The discovery of different PSA molecular forms in serum (free PSA, PSA complexed with various protease inhibitors) in the early 1990s renewed clinical research to enhance the specificity of PSA. Also, the use of a homologous prostate-localised antigen, human glandular kallikrein 2 (KLK2) may further reduce the number of unnecessary prostate biopsies. More recently, promising data is emerging regarding molecular forms of free PSA (proPSA, BPSA, 'intact' PSA) and other members of the expanded human kallikrein family. These new findings may add substantial clinical information for early detection of prostate cancer.