Infertility is defined as inability of establishing clinical pregnancy after 12 months of regular unprotected intercourse and it affects approximately 10% of couples in their reproductive years. The factors of infertility and reduced fertility are numerous, either female, male or combined. Accurate embryonic and fetal development of reproductive tissues and germ cells, maintenance of their integrity in adulthood, as well as proper cellular steps during gametogenesis regulated by hypothalamic-pituitary-gonadal axis, are all indispensable for the normal function of reproductive system in both sexes. All of these processes are dependent on adequate gene expression, which arises from the interplay of underlying nucleotide sequence and its associated epigenomic pattern that modulates phenotypic expression without any genotypic alteration. Any genomic or epigenomic irregularity of somatic gonadal cells has the potential to disturb sex determination and differentiation with consequential occurrence of disorders of sex development (DSD). On the other hand, irregularities of germ cells lead to defects of gametogenesis, gamete maturation processes , fertilization or early embryonic development with manifestation as fertilization failure, preimplantational arrest or transmission of genetic and/or epigenetic modifications to the offspring with subsequent development of congenital diseases or susceptibility to certain diseases in adulthood. The aim of this review is to evaluate genetic and epigenetic factors underlying infertility and subfertility so as to better appreciate the heterogeneity of their etiology.