Serum prostate-specific antigen (PSA) measurements are the most useful serum biomarker to aid in early prostate cancer detection, clinical staging and therapeutic monitoring. Although the optimal use of PSA testing remains controversial, population based studies suggest that PSA screening reduces prostate cancer mortality. Customizing screening protocols based on individual risk factors and PSA level may be a useful approach to reduce overall costs incurred by widespread PSA testing. Lowering PSA cut-offs (i.e., from 4.0 ng/ml to 2.5 ng/ml) may reduce advanced stage prostate cancer, and the use of different PSA derivatives and PSA forms may reduce 'unnecessary' biopsies in some men. In addition to prostate cancer, manipulation and benign diseases of the prostate falsely elevate serum PSA levels. In contemporary clinical practice, PSA testing plays an important role in prostate cancer diagnosis and treatment.