The presence of steroid binding sites in (or on) human spermatozoa was first suggested in the late 1970s, by studies showing that some steroids were able to influence sperm function. Subsequently, several effects exerted on spermatozoa by biological fluids, such as follicular fluid, were found to be probably linked to the action of steroids, and among them progesterone. Since the effects of progesterone on spermatozoa were rapid, dose-dependent and not affected by progesterone conjugation with high molecular weight proteins unable to cross the plasma membrane, the existence of a novel class of non-genomic progesterone receptors was strongly suspected. This hypothesis was further supported by the observation that some of the effects of progesterone on human spermatozoa were not abolished by inhibitors of the classical progesterone nuclear receptors, nor mimicked by progesterone genomic receptor agonists. Recently, surface progesterone binding sites were directly identified on the membranes of human spermatozoa, and their mechanism of action partially characterized.