Puberty is triggered by a complex neuroendocrine mechanism that leads to an increase in GnRH release at the end of the childhood and, hence, to reactivation of the gonadotropic axis. Recent human genetic studies have led to major breakthroughs in our understanding of puberty onset. A network of hypothalamic neurons controlling GnRH release has just been characterized. It appears that the timing of puberty onset is under the control of the heterochronic gene Lin28, which encodes a protein regulating microRNA maturation. Characterization of additional gene defects associated with abnormal puberty onset is needed to further characterize this neuroendocrine network and to identify new therapeutic targets for reproductive disorders.