This narrative review summarizes the state of the evidence about the phenomenon of health-related quality of life (HRQOL) among survivors of childhood cancer. A major strength of the state of the evidence on the HRQOL among survivors of childhood cancer is the availability and quality of the data generated from the Childhood Cancer Survivor Study (CCSS). Findings from most studies find comparable levels of HRQOL among survivors and constructed cohort samples; however, a poorer level of HRQOL exists among female survivors. Factors that predict a lower or poorer level of HRQOL among survivors include age at diagnosis, age attained, time since diagnosis, socioeconomic status (education level, household income, and employment status), physical role functioning, and health insurance. Those survivors who received cranial radiation, especially survivors of central nervous system tumors, are at an increased risk for poorer HRQOL and long-term negative effects.