Nitric oxide (NO), a member of the reactive nitrogen species family, plays a role in several physiologic processes, including vasculogenesis and angiogenesis, growth and puberty, and senescence and apoptosis. NO plays an important role in the production of ovarian steroids, ovulation, and follicular apoptosis. In other words, increased activity of nitric oxide synthase (NOS) leads to an increased amount of NO, which triggers production of prostaglandins and inflammatory cascades which facilitate follicular rupture and atresia. NO concentration elevation inhibits steroid synthesis in luteal and granulosa cells. Since NO is a major paracrine mediator of various biological processes, as well as a key factor in both the reproductive cycle and embryo implantation, oversynthesis of NO in the uterus results in toxicity and inflammation in epithelial cells and immunorejection of implantation. In the male physiological system, NO synthesized by NOS plays a major role in erectile function and androgen secretion, as well as semen parameters, and oocyte junction to the sperm. Furthermore, this supposedly simple molecule is involved in a number of other functions, such as germ cell evolution, connections between sertoli cells and germ cells in the blood-testis barrier, homodynamic contraction, and germ cell apoptosis. Moreover, NO is considered a key factor in male fertility due to its widespread distribution in both normal and diseased testis tissue. The difference of expression level of NOS in normal and pathological states is a probable cause of fertility destructive processes.