Regucalcin (RGN) is a calcium (Ca(2+))-binding protein which plays an important role in the regulation of Ca(2+) homeostasis and has been shown to catalyse an important step in L-ascorbic acid biosynthesis. It is encoded by an X-linked gene and differs from other Ca(2+)-binding proteins by lacking the typical EF-hand Ca(2+)-binding domain. RGN controls intracellular Ca(2+) concentration by regulating the activity of membrane Ca(2+) pumps. Moreover, RGN has been indicated to regulate the activity of numerous enzymes and to act in the regulation of cell proliferation and apoptosis. The importance of Ca(2+) homeostasis in spermatogenesis has been demonstrated by several studies, and its disruption has been shown to cause reversible male infertility. Recently, the expression of RGN in male reproductive tissues has been described and its localization in all testicular cell types was demonstrated. In addition, RGN expression is regulated by androgens, a class of steroid hormones recognized as male germ cell survival factors and of uttermost importance for spermatogenesis. Altogether, available information suggests the hypothesis that RGN might play a role in spermatogenesis, directly or as a mediator of androgen action. This review discusses this hypothesis presenting novel data about RGN expression in human testis.