The beginning of embryogenesis is preceded by a sequence of events mediated by the release of intracellular calcium in the ooplasm, a multifaceted process known as oocyte activation. It is now well established that a sperm protein factor introduced into the oocyte at the time of gamete fusion is responsible for initiating the cascade of signaling events involved. Several sperm proteins have been hypothesized as the sperm oocyte-activating factor (SOAF) over the years, with phospholipase C zeta 1 (PLCZ1 or PLCzeta) emerging as the strongest candidate. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, has accumulated in support of PLCzeta, and data clearly demonstrate that oocyte activation ability can be rescued in PLCzeta-deficient sperm by either PLCzeta cRNA or recombinant PLCzeta protein. However, a series of recent publications has challenged the dominance of PLCzeta and proposed an alternative candidate protein, WBP2 N-terminal like (WBP2NL or PAWP). These events have led to significant debate, fueled by the opposing views of two independent laboratories, each defending its own respective SOAF candidate. This raises important questions with regards to the relative importance of these two proteins in diagnostic and therapeutic medicine, and invites urgent research attention. Here, it is our intention to reflect upon this now very controversial area in order to engage the scientific and clinical communities in addressing the true importance of these two sperm proteins.