Human puberty begins with the reemergence of GnRH secretion from its relative quiescence during childhood, activating a cascade of pituitary-gonadal maturation. This transition begins across a wide range of ages, and the rate of subsequent sexual maturation can be quite varied. The factors that regulate the hypothalamic-pituitary-gonadal axis and modulate the timing of puberty remain elusive, but it is clear that some regulation is under genetic control. Here, we discuss how new advances in genetic research may provide the tools to help unravel this long-standing mystery.