Spermatozoa produced in the testis undergo maturation in the epididymis which secretes an osmolyte-rich fluid that bathes the sperm cells. These cells need to maintain their volume after ejaculation when they first encounter hypo-osmolal environments of accessory gland fluids and later within the female tract. If they do not, they experience swelling that is manifested in flagellar angulation that prevents their passage through cervical mucus or the uterotubal junction and they never reach the oocytes. This is a cause of male infertility in domestic species and certain infertile transgenic mice in which flagellar angulation has been shown to indicate cell swelling as a consequence of reduced epididymal provision of osmolytes. The reduced volume regulating ability of spermatozoa from subfertile boars and bulls has prompted study of volume regulation of spermatozoa as a possible cause of human male infertility. Understanding this process may make its manipulation possible and could suggest better sperm handling and storage techniques and thus provide therapy for infertile patients. On the other hand, volume regulation is a potential target for contraception if mimicking the conditions expressed by the “sterile studs” were possible. The evidence for the presence of ion channels probably responsible for regulatory volume decreases in spermatozoa is reviewed here that implicate voltage-gated potassium channels (especially Kv1.5 (KCNA5), minK (KCNE1) and TASK2 (KCNK5)) and the chloride channels CLCN3 and CLNS1A. The involvement of ion co-transporters in volume regulation of spermatozoa is also discussed.