The purpose of this chapter is to provide a comprehensive overview of spermatogenesis and the various steps involved in the development of the male gamete, including cellular processes and nuclear transformations that occur during spermatogenesis, to provide a clear understanding of one of the most complex cellular metamorphosis that occurs in the human body. Spermatogenesis is a highly complex temporal event during which a relatively undifferentiated diploid cell called spermatogonium slowly evolves into a highly specialized haploid cell called spermatozoon. The goal of spermatogenesis is to produce a genetically unique male gamete that can fertilize an ovum and produce offspring. It involves a series of intricate, cellular, proliferative, and developmental phases. Spermatogenesis is initiated through the neurological axis by the hypothalamus, which releases gonadotropin-releasing hormone, which in turn signals follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to be transmitted to the reproductive tract. LH interacts with the Leydig cells to produce testosterone, and FSH interacts with the Sertoli cells that provide support and nutrition for sperm proliferation and development. Spermatogenesis involves a series of cell phases and divisions by which the diploid spermatogonial cells develop into primary spermatocytes via mitosis. Primary spermatocytes in the basal compartment of Sertoli cells undergo meiosis to produce haploid secondary spermatocytes in the adluminal compartment of Sertoli cells in a process called spermatocytogenesis. This process gives the cells a unique genetic identity within the population of secondary spermatocytes and subsequent developing cells. After spermatocytogenesis, spermatids elongate to form spermatozoa by spermiogenesis, a morphological development phase in which the nuclear transformations involving chromatin remodeling and compaction occur. Spermatozoa then leave the Sertoli cells through the lumen of the seminiferous tubules, exit through the rete testis, and enter the epididymis for final maturation. This is where spermatozoa acquire motility and acrosomal function. Spermatogenesis in the human male takes about 74 days. Spermatogenesis is regulated by intrinsic and extrinsic factors. Not all spermatogonia mature into spermatozoa – most are eliminated and phagocytosed in a process called apoptosis. The overall goals of spermatogenesis are (1) to enable the male to transfer genetically recombined DNA by contributing to half of the offspring’s genome and (2) to equip the spermatozoa to effectively navigate through the female reproductive tract and deliver the genetic material to the ovum. In the following sections, the complex transformation of the simple single diploid cell into a fully functional haploid cell is described.