An association between age and prostate-specific antigen (PSA) has been documented: As men age, their serum PSA value increases. Currently, a single demarcation between normal and elevated PSA values, 4.0 ng/mL, is used as an indication for biopsy among men of all ages. The use of age-specific reference ranges might address several shortcomings of the PSA test. First, age-specific reference ranges could improve the sensitivity of PSA by detecting curable, organ-confined tumors in younger men when the threshold of 4.0 ng/mL is lowered. Second, age-specific reference ranges could improve the specificity of the PSA test by raising the PSA threshold for normal among older men. This would modulate PSA interpretation by taking into account the increasing prevalence of both benign prostatic growth and incidental, non-life-threatening cancers among successively older cohorts of men. Furthermore, many unnecessary (false-positive) biopsies would be avoided. However, the association between PSA values and age is not entirely clear, and whether age-specific reference ranges represent the best interpretive index for PSA remains problematic.