The ability to select high fertility sires results in the production of semen samples with optimal quality that will, ultimately improve conception rates. Currently, routine semen analysis based on motility and morphology provide useful, but limited information about fertility indexes in the male. Proven, high-use bulls from artificial insemination centers still show differences in non-return rates by as much as 20 to 25 %. The existence of subfertile sires with apparent normal semen quality is an important observation and has stimulated the search for other markers of fertility. Killian et al. (1993) reported the presence of four “fertility-associated proteins” in the Holstein seminal plasma, one of them later identified as osteopontin (OPN). The same protein, detected in accessory sex gland fluid, was associated with fertility indexes of dairy bulls. Osteopontin was first described in mineralized bone tissues as a cell adhesion component and its functions include cell migration, chemotaxis, calcification, tumor growth, and macrophage activation. This ubiquitous protein is expressed in the ampullae, seminal vesicles and possibly the epididymis, as well as in the oviduct. In the seminiferous tubules, where it is synthesized by Sertoli and germ cells, OPN is potentially involved in cell adhesion and migration. This review, therefore, summarizes key aspects of the osteopontin structure and expression in the male, and supports the notion that OPN plays a role in sperm-egg binding and fertilization.