The largest segment of missing children in the United States includes runaways, children who run away from home, and thrownaways, children who are told to leave or stay away from home by a household adult. Although estimates vary, as many as 1 in 20 youth run away from home annually. These unaccompanied youth have unique health needs, including high rates of trauma, mental illness, substance use, pregnancy, and sexually transmitted infections. While away, youth who run away are at high risk for additional trauma, victimization, and violence. Runaway and thrownaway youth have high unmet health care needs and limited access to care. Several populations are at particular high risk for runaway episodes, including victims of abuse and neglect; lesbian, gay, bisexual, transgender, and questioning youth; and youth in protective custody. Pediatricians and other health care professionals have a critical role to play in supporting runaway youth, addressing their unique health needs, fostering positive relationships within their families and with other supportive adults, and connecting them with available community resources. This report provides clinical guidance for pediatricians and other health care professionals regarding (1) the identification of adolescents who are at risk for running away or being thrown away and (2) the management of the unique medical, mental health, and social needs of these youth. In partnership with national, state, and local resources, pediatricians can significantly reduce risk and improve long-term outcomes for runaway youth.