Experimental evidence from the last 30 years supports the fact that the oviduct is involved in the modulation of the reproductive process in eutherian mammals. Oviductal secretion contains molecules that contribute to regulation of gamete function, gamete interaction, and the early stages of embryo development. The oviductal environment would act as a sperm reservoir, maintaining sperm viability, and modulating the subpopulation of spermatozoa that initiates the capacitation process. It could also contribute to prevent the premature acrosome reaction and to reduce polyspermy. Many studies have reported the beneficial effects of the oviductal environment on fertilization and on the first stages of embryo development. Some oviductal factors have been identified in different mammalian species. The effects of oviductal secretion on the reproductive process could be thought to result from the dynamic combined action (inhibitory or stimulatory) of multiple factors present in the oviductal lumen at different stages of the ovulatory cycle and in the presence of gametes or embryos. It could be hypothesized that the absence of a given molecule would not affect fertility as its action could be compensated by another factor with similar functions. However, any alteration in this balance could affect certain events of the reproductive process and could perhaps impair fertility. Thus, the complexity of the reproductive process warrants a continuous research effort to unveil the mechanisms and factors behind its regulation in the oviductal microenvironment.