In about 50% of the couples trying to conceive, a male factor is responsible. Gonadotropins in hypogonadotropic hypogonadism as well as anti-inflammatory drugs and antibiotics in selected cases are medical agents with proven effectiveness. However, 30-40% of men presenting with infertility are ultimately labelled as having idiopathic infertility, with no identifiable cause. Although these men present with no previous history of diseases affecting fertility and have normal findings on physical examination and routine endocrine, genetic and biochemical laboratory testing, capacity of the conventional seminal analysis and hormonal findings to predict reproductive potential is limited. However currently introduced other additional screening tools, such as oxidative stress and sperm DNA damage, as well as epigenomic and proteomic biomarkers, metabolomic profiling may reveal some specific pathological findings and help to predict fertility potential in a more accurate manner. For this reason treatment of an infertile man should be planned by using an analytic perspective regarding such developments. This allows a customized therapeutic strategy. Different protective and treatment regimens may be offered to eliminate detrimental outcomes of reactive oxygen species, epigenetic modifications, endocrine disruption as a result of environmental pollution, etc. Also, next-generation sequencing (NGS) test has contributed to the identification of novel genes responsible for fertility potential and gives the opportunity to make key decisions in the management of infertile patients.