Prostaglandins (PGs) are derived from arachidonic acid by action of the cyclooxygenase (COX) isoenzymes COX1 and COX2. The development of mice deficient in COX1 and/or COX2 has shown that COX2–null female mice are infertile. In contrast, male fertility is not affected in COX1- or COX2-mutant mice from knock-out experiments, suggesting that PGs may not be important for the functioning of the testis. This early general view is being challenged by recent observations. We have reported that whereas COX2 is not detected in normal human testes, it is expressed in testicular biopsies of men with impaired spermatogenesis and male infertility. Moreover, COX is up-regulated in testicular cancer, and COX2 expression is induced in Brown-Norway rat Leydig cells during aging. Several reports describe actions of COX and PGs on steroid hormone production, expression of PGs and their receptors in Sertoli cells, and inhibitory effects of some PGs on spermatogenesis and sperm counts. In brief, this review summarizes the results obtained in the last decades by our laboratory and other groups that point out the impact of COX and PGs in the regulation of testicular function and male fertility.