In mammals, eggs exhibit a series of transient increases in intracellular calcium ion (Ca² ) concentrations (Ca² oscillations) at the time of fertilization, which are prerequisite and sufficient for egg activation. Recent studies have been revealing the molecular mechanism of how sperm induce Ca² oscillations in fertilized eggs, that has remained unclear for a longtime. Especially in mammals, the sperm factor theory is being confirmed, which postulates that a cytoplasmic factor in the spermatozoon (the “sperm factor”) is introduced into the egg through the sperm-egg cytoplasmic connection and activates the egg. In 2002, a new isoform of phospholipase C (PLC), PLC zeta, was identified as a strong candidate for the mammalian sperm factor. In this mini-review, the history of the mammalian sperm factor theory and the search for the mammalian sperm factor is reviewed. In addition, whether PLC zeta is truly the mammalian sperm factor or not is discussed.