Genetics forms the most important factor in the complex of etiological factors contributing to human infertility. The enormous role of genetics in the wide spectrum of fertility ranging from sex determination, direction of gonadal development in early fetal life, development of primary sex organs and sexual characteristics, gametogenesis, hormonal homeostasis, fertilization and implantation to epigenetics, necessitates the need for in-depth understanding and application of cytogenetics, molecular tools, and epidemiological studies in the treatment of an infertile couple. This chapter covers the role of genetics in infertility, basics of cytogenetics, role of genetics in male infertility, chromosomal abnormalities, gene polymorphism and male infertility, autosomal gene mutations and male infertility, x-linked genes, genetics of female infertility, and chromosomal aberrations.