The testes synthesize two important products: testosterone, needed for the development and maintenance of many physiological functions; and sperm, needed for male fertility. The synthesis of both products is regulated by endocrine hormones produced in the hypothalamus and pituitary, as well as locally within the testis. Testosterone is indispensable for sperm production, however both testosterone and Follicle Stimulating Hormone (FSH) are needed for optimal testicular development and maximal sperm production. Sperm are produced via the extraordinarily complex and dynamic process of spermatogenesis that requires co-operation between multiple testicular cell types. While it has long been known that testosterone and FSH regulate spermatogenesis, years of research has shed light on many of the intricate mechanisms by which spermatogonial stem cells develop into highly specialized, motile spermatozoa. Spermatogenesis involves the concerted interactions of endocrine hormones, but also many paracrine and growth factors, tightly co-ordinated gene and protein expression programs as well as epigenetic modifiers of the genome and different non-coding RNA species. This chapter provides a comprehensive overview of the fascinating process of spermatogenesis and of its regulation, and emphasises the endocrine regulation of testicular somatic cells and germ cells. The chapter also provides a summary of the clinically significant aspects of the endocrine regulation of spermatogenesis. For complete coverage of all related areas of Endocrinology, please see our online FREE web-book, www.endotext.org.