The capacity for sperm storage within the female reproductive tract occurs widely across all groups of vertebrate species and is exceptionally well developed in some reptiles (maximum duration seven years) and fishes (maximum duration >1 year). Although there are many reports on both the occurrence of female sperm storage in diverse species and its adaptive benefits, few studies have been directed toward explaining the mechanisms involved. In this article we review recent findings in birds and mammals in an effort to develop hypotheses that could be translated into research applications in animal breeding technologies. There are pockets of evidence to suggest that the local epithelial cells, sometimes arranged as sperm storage tubules, can respond to spermatozoa by producing heat shock proteins as well as providing an environment rich in antioxidants. Moreover, the local immune system seems to tolerate the arrival of spermatozoa, while retaining the ability to combat the arrival of infectious microorganisms.