Juvenile-onset systemic sclerosis (jSSc) is a complex multisystem inflammatory-driven disease of fibrosis, requiring multifaceted treatment including pharmacologic therapy, supportive care, and lifestyle modification. Most regimens are adapted from adult SSc treatment given the rarity of the disease. Landmark trials over the past decade in adult SSc have led to 2 Food and Drug Administration–approved therapies for SSc-associated interstitial lung disease, and several ongoing trials of other biological agents are underway. Resetting the immune system with autologous stem cell transplant to halt this disease earlier in its course, especially in pediatric onset where disease burden can accumulate, is on the horizon.