Photoperiod, food availability, temperature, stress, and hormonal cues are some of the varied signals used by mammalian species to activate or suppress their timing of sexual maturation. All ultimately converge upon gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Through its stimulation of LH and FSH from the pituitary, GnRH represents a critical step in the reproductive cascade. While few dispute this central role of GnRH, little is understood of the mechanisms influencing the developmental fate and physiologic controls of GnRH neurons. Identification of the signals which modulate pulsatile GnRH secretion is critical to advancing understanding of normal puberty and reproductive competency. The recent identification of loss-of-function mutations in GPR54, a receptor for kisspeptin-1, has highlighted a new pathway for the timing of puberty and reproductive control.