The 14-3-3 (YWHA or Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation protein) is an acidic and homologous protein family involved in regulation of key biological events including cell cycle, signal transduction and development. They are highly conserved and are expressed ubiquitously across a wide variety of species ranging from plants to animals. Seven isoforms of 14-3-3 exist in mammals, which are encoded by separate genes, have tissue-specific, developmental stage-specific as well as isoform-specific presence and consequences. It is known that these proteins play significant roles in mitosis of mammalian cells and meiosis of amphibians. However, their effects on development and functioning of mammalian gonads and germ cells are not entirely delineated. This paper, for the first time, provides a comprehensive review of the comparative expression, localization/distribution, binding interactions, and importance of the 14-3-3 proteins in gametogenesis and reproduction among multiple female and male mammalian species. Thorough understanding of these proteins in oogenesis and spermatogenesis would help elucidate the physiological basis of fertility in mammals, including humans.