Progesterone's (P) stimulatory actions on human spermatozoa have been known for many years. P indeed appears to be the main sperm stimulator present in women's biological fluids, particularly the follicular fluid. The nongenomic nature of the biological effects of P on human spermatozoa has been demonstrated only recently. P and 17-alpha-hydroxy P have been shown to increase sperm intracellular calcium, phosphatidylinositide hydrolysis, and tyrosine phosphorylation of proteins, and to induce the acrosome reaction (AR), through a rapid, nongenomic mechanism. The effect on calcium is due to influx of the ion from the extracellular medium, as it is inhibited by the calcium chelator EGTA and appears to be mediated by P-binding sites present on the sperm surface, particularly at the head level. The nature of such binding sites has not been addressed so far, but the lack of inhibition of P action by the potent antiprogestin RU486 strongly suggests a biochemical difference from the genomic ones. Evidence exists for involvement of the phospholipid platelet-activating factor (PAF), polyamines, tyrosine kinase activation, proteases, and other factors in P-mediated calcium increase and acrosome reaction. Recent studies suggest the possibility that the sperm's response to P may be functionally related to their fertilizing ability, thus opening new perspectives in the possible development of a predictive test in the assisted reproductive techniques.