Gender-nonconforming youth are emerging at increasingly younger ages, and those experiencing gender dysphoria are seeking medical care at, or sometimes even before, the onset of puberty. Youth with gender dysphoria are at high risk for depression, anxiety, isolation, self-harm, and suicidality at the onset of a puberty that feels wrong. Medical providers would benefit from understanding interventions that help gender-nonconforming children and youth thrive. The use of gonadotropin-releasing hormone (GnRH) agonists to block the onset of an undesired puberty in youth with gender dysphoria is a relatively new practice, particularly in the United States. These medications shut down the hypothalamic-pituitary-gonadal axis (HPG), and the production of either testosterone or estrogen is temporarily halted. Puberty blocking allows a young person to explore gender and participate more fully in the mental health therapy process without being consumed by the fear of an impending developmental process that will result in the acquisition of undesired secondary sexual characteristics. GnRH agonists have been used safely for decades in children with other medical conditions, including central precocious puberty. Potential side effects of GnRH agonists include diminished bone density, injection site problems, emotional instability, and weight gain. Preliminary data have shown GnRH agonists to be very helpful in improving behavioral and overall functioning outcomes. Puberty suppression should ideally begin in the first stages of pubertal development and can be given via intramuscular or subcutaneous injections, or via an implant that is inserted in the upper arm. Monitoring to assure suppression of the HPG axis should occur regularly. Gender-nonconforming youth who remain gender dysphoric can go on to receive cross-sex hormones for phenotypic gender transition when they are older. GnRH agonists have changed the landscape of medical intervention for youth with gender dysphoria and are rapidly becoming the standard of practice.