Spermatogenesis is a unidirectional process ultimately giving rise to one of the most specialized cell types in the body, the sperm. However, spermatogenesis also has a cyclic nature, and cell associations of a constant composition are repetitively observed after a fixed, species-dependent interval - known as the seminiferous cycle. In the testicular seminiferous tubules, formation of cellular associations of constant composition, or stages, is the outcome of synchronous development of spermatogenic cell cohorts. Cyclical turnover of spermatogenic cell cohorts coincides with cyclic function of Sertoli cells, the somatic supporting cells. Sertoli cells transduce endocrine and paracrine stimuli into local regulation of spermatogenesis in a stage-dependent manner, and are therefore the key regulators of the seminiferous cycle. In the immature testis, Sertoli cells induce the onset of spermatogenesis, whereas in the adult testis spermatogenic cells maintain the seminiferous cycle, and adjust the Sertoli cell ‘clock’. While cyclicity is an inherent property of Sertoli cells, guidance from spermatogenic cells is required for it to be fully manifested. Paracrine retinoic acid (RA) has a key role at the onset of spermatogenic differentiation, but testosterone and FSH (follicle-stimulating hormone) are required for quantitatively and qualitatively normal spermatogenesis. RA, testosterone and FSH exert their effects on spermatogenesis in a stage-dependent manner. While the mechanism behind the stage-dependent action of RA is the restriction of its availability, seminiferous cycle-dependent receptor expression explains the stage-reliance of testosterone and FSH action.