Differentiation of stem cells into spermatogenic lineages in vitro provides a unique window into the biological mechanisms responsible for driving pluripotent stem cells into essential progeny-haploid spermatids and viable sperm-as well as provides an innovative approach for determining novel root causes for male infertility. Our recent work outlined a novel approach for differentiating human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) into advanced spermatogenic lineages including haploid spermatids with correct parentof-origin genomic imprints on two loci. The work described here in this chapter provides a foundation for building a true in vitro model for human spermatogenesis with which to model, diagnose and potentially treat male factor infertility.