In mammals, the role of sperm in the process of fertilization is complex, and several well-defined steps must occur for the sperm to fertilize with the oocyte. Phospholipases (PLs), which regulate the lipid composition of the sperm by hydrolyzation of the phospholipids, are involved in the regulation of the flagellar beat, capacitation, and the acrosomal reaction, as well as in the triggering of the calcium oscillations in the oocyte that lead to oocyte activation. The emerging important role of phospholipases is also revealed by the fact that alterations of sperm lipids can lead to infertility. Phospholipases, especially PLCζ, could represent therapeutic targets to overcome male infertility.