The mammalian Y chromosome, once thought to be a genetic wasteland, is now known to encode a battery of genes, many of which are thought to be involved in male reproduction. A substantial amount of work has been done to define which genes are important for maintaining sperm function under normal, in vivo, conditions. In the era of assisted reproduction technologies (ART), however, it is possible to bypass several steps of normal fertilization using immotile, nonviable, or even immature sperm. Consequently, in the context of ART, the essential roles of the Y chromosome genes may become abrogated. We have shown that live offspring can be obtained from mice lacking the entire Y chromosome long arm, in which the Y chromosome was reduced from 78 Mb to ~2 Mb and encoded only 7 genes and 3 gene families. We also demonstrated that live offspring can be generated using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y. Sry is believed to function primarily in sex determination during fetal life. Eif2s3y may therefore be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. If so, what is the importance of the Y chromosome in male reproduction? The answer lies in defining the need. The Y genes are undoubtedly needed for many aspects of reproduction involving the development of mature sperm and its function in normal fertilization. However, when it comes to ART, the Y chromosome contribution can be brought to a bare minimum of Sry and Eif2s3y. Indeed, it may well be possible to eliminate mouse Y chromosome altogether if appropriate replacements are made for those two genes. (Supported by NIH HD072380, HD058059, GM103457 and Hawaii Community Foundation).