A series of receptor signaling pathways potentially govern chemical communication between sperm and egg, chemotactically guiding incoming sperm towards the oocyte. Though several substances are confirmed as sperm chemoattractant, progesterone (P) seems to be the best chemoattractant candidate for human sperm. Ion channels control the sperm ability to fertilize the egg by regulating sperm maturation in the female reproductive tract and by triggering key sperm physiological responses required for successful fertilization such as hyperactivated motility, chemotaxis, and the acrosome reaction. CatSper, a pH regulated, calcium selective ion channel, potassium channel KSper (Slo3), and Hv1, the voltage gated proton channel are involved in regulation of sperm hyperactivated motility. While progesterone, secreted by ovulated cumulus oophorus, may act as a chemoattractant for sperm cells over the short distances, a major determinant of sperm guidance over long distances in the mammalian female reproductive tract is rheotaxis.