The diagnostic and prognostic validity of sperm function biomarkers is particularly relevant for males with unexplained infertility in which routine semen analysis fails to detect subcellular sperm dysfunctions. In this general review, we examine the role and significance of specialized andrology laboratory tests from past to present and provide a glance toward the future. We concluded that the assessment of sperm DNA damage and oxidative stress provide a relatively independent measure of fertility that yields diagnostic and prognostic information complementary to, but distinct and more significant than, standard sperm parameters. Since none of the available methods for such testing have been fully translated, further research is necessary to evaluate their cost-effectiveness when applied in large scale to daily medical practice. Application of translational medicine concepts would also be useful to accelerate the clinical application of recent discoveries in the fields of genomics, proteomics and metabolomics.