The male factor is responsible for about 40% of couple infertility cases and such percentage is expected to increase in the future because of several likely factors including the presence of endocrine disruptors in the environment,changes in lifestyle habits and advanced couple aging.How such factors affect male fertility status,however,should be clarified.Most studies on male fertility status have focused on parameters analyzed using a spermiogram test,the primary diagnostic tool in the routine assessment of male infertility,which is,however,poorly predictive of both natural and medically assisted conception.For these reasons it is mandatory for the scientific community to identify new molecular markers to incorporate into the existing diagnostic tests of male fertility.Ideally,such markers would be detected in mature spermatozoa to avoid invasive procedures for the patient.This review summarizes the recent advancements in benchside approaches that appear most promising for the development of new diagnostic sperm fertility tests,or identification of therapeutic targets,and,illustrates their advantages and limits. The male factor is responsible for about 40% of couple infertility cases and such percentage is expected to increase in the future because of several likely factors including the presence of endocrine disruptors in the environment, changes in lifestyle habits and advanced couple aging. Howard such factors affect male fertility status, however, should be clarified. Most studies on male fertility status have had focused on parameters analyzed using a spermiogram test, the primary diagnostic tool in the routine assessment of male infertility, which is, however, poorly predictive of both natural and medically assisted conception.For these reasons it is mandatory for the scientific community to identify new molecular markers to incorporate into the existing diagnostic tests of male fertility. Ideally, such markers would be detected in mature spermatozoa to avoid invasive procedures for the patient. This review summarizes the recent advancements in benchside approaches that appear most promising for the develo pment of new diagnostic sperm fertility tests, or identification of therapeutic targets, and, illustrate their advantages and limits.