Globozoospermia is a severe teratozoospermia, and the cases with 100% round-headed sperm are rare clinically. Globozoospermia is generally characterized by absence or abnormality of acrosome, accompanied by round-headed sperm with deranged midpiece and tails. The acrosome normally contains the enzymes that enable sperm to fertilize oocytes, while defective sperm cannot independently fertilize oocytes either in vivo or in vitro, and therefore globozoospermia makes males infertile clinically. Recent studies show that the deletion of the DPY19L2 (dpy-19-like 2) gene is a major cause of globozoospermia. This paper updates the relationship between DPY19L2 and globozoospermia to provide some evidence for further studies on the gene diagnosis and molecular mechanisms of globozoospermia.