Infertility is currently regarded as a male or female-dependent pathologic condition. However, emerging evidence suggests that this may be an incomplete view as it misses the important fact that the gametes of some males and females often have higher compatibility than others. In this article, I present recent evidence demonstrating that female reproductive tract secretions in humans mediate “mate choice” at the level of the gametes, and this way likely bias fertilization toward immunologically or otherwise compatible males. A better understanding of this evolutionary selection process may open up novel possibilities for the future development of more personalized infertility diagnostics and treatments.