At fertilisation, fusion of the sperm with the oocyte activates a slew of downstream processes to kick-start embryogenesis. This ‘oocyte activation’ event induces the cortical reaction to prevent polyspermy, triggers oocyte metabolic and DNA synthesis pathways, and reactivates meiosis. In mammals, there is evidence to suggest that a phospholipase C isoform, PLCζ, initiates calcium oscillations associated with oocyte activation when delivered from sperm to egg. Hence, PLCζ is thought to be crucial for the activation process. Here, on p. 2914, John Parrington and colleagues directly test this hypothesis using CRISPR/Cas9 to generate a PLCζ knockout mouse. They report that while the production and quality of sperm are unaffected in knockouts, the sperm fail to induce calcium waves at fertilisation, confirming that PLCζ is required for this event. Intriguingly, although the majority of eggs fertilised by the knockout sperm do not develop, some are able to initiate embryogenesis, albeit in a delayed manner. Remarkably, PLCζ knockout mice could father a small number of offspring that develop to term, suggesting that oocyte activation can occur via an alternative route when PLCζ-triggered calcium oscillations fail. These findings will provoke further investigation into what this alternative mechanism might be, and the PLCζ knockout will be a useful tool to study infertility in mammals.